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Shauku Huang - One of the best experts on this subject based on the ideXlab platform.
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clara cell 10 kda protein inhibits th17 responses through modulating dendritic cells in the setting of allergic rhinitis
The Journal of Allergy and Clinical Immunology, 2013Co-Authors: Hai Jing Yu, Shauku Huang, Nan Wang, Ya Na ZhangAbstract:Background T H 17 responses have recently been implicated to play a role in allergic airway diseases, but their local expression in the setting of allergic rhinitis (AR) and their regulation in allergic airway diseases remain unclear. Objective We sought to investigate the regulatory role of Clara cell 10-kDa protein (CC10), an endogenous regulator of airway inflammation, on T H 17 responses in the setting of AR. Methods Wild-type and homozygous CC10-null mice were used to establish an ovalbumin (OVA)–induced AR model. Human recombinant CC10 was given during sensitization or challenge. T H 17 responses in human subjects and mice were examined by using flow cytometry, quantitative RT-PCR assay, immunohistochemistry, and ELISA. The direct effect of CC10 on T H 17 cells and CD11c + dendritic cells (DCs) was studied by means of cell culture. Adoptive transfer was used to examine the influence of CC10-conditioned DCs on airway inflammation. The regulatory effect of CC10 on the expression of the CCL20 gene was tested by using the BEAS-2B cell line. Results Compared with those of control subjects, T H 17 responses were enhanced in the nasal mucosa of patients with AR. CC10-null mice with AR showed enhanced T H 17 responses, and CC10 treatment significantly decreased T H 17 responses. CC10 had no direct effect on in vitro T H 17 cell differentiation. CC10 could significantly decrease the expression of OX40 ligand, IL-23, and IL-6 but enhance CD86 and TGF-β expression in DCs. Importantly, CC10 was able to inhibit T H 17 cell polarization in the presence of OVA-pulsed DCs. CC10 pretreatment inhibited T H 17 responses elicited by adoptive transfer of OVA-pulsed DCs. Furthermore, CC10 decreased the expression of CCL20 in BEAS-2B cells induced by inflammatory cytokines. Conclusion T H 17 responses are enhanced in patients with AR, and CC10 inhibits T H 17 responses through modulation of the function of DCs.
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the expression of osteopontin and its association with clara cell 10 kda protein in allergic rhinitis
Clinical & Experimental Allergy, 2010Co-Authors: Xiang Lu, Hai Jing Yu, Shauku HuangAbstract:Summary Background Osteopontin (OPN) is a multifunctional protein that has recently been linked to allergic diseases. Clara cell 10 kDa protein (CC10) is another protein linked to allergy, and has been suggested to have an inhibitory role in inflammatory airway diseases. At this time, it is not known whether OPN is involved in allergic rhinitis (AR) or if there is any association between CC10 and OPN in AR. Objective To study the expression of OPN and its potential association with CC10 in AR. Methods The expression of CC10 and OPN in nasal mucosa of AR patients was investigated. AR animal models were established by using wild-type and CC10-knockout mice. In some experiments, human recombinant CC10 protein was given to AR mice during either sensitization or challenge. The phenotypic changes were examined by histology and real-time RT-PCR. The direct effect of CC10 on the OPN expression in spleen mononuclear cells and on the OPN-induced inflammatory cytokine expression in BEAS-2B cells was measured through in vitro cell culture. Results OPN expression was up-regulated, with a concomitant down-regulation of CC10, in AR patients, showing a significant negative correlation between their expression. Compared with control mice sensitized with PBS, the OPN expression was significantly increased in AR mice; such an increase was more prominent in CC10-knockout mice, compared with wild-type. Administration of CC10 during both sensitization and challenge could markedly ameliorate Th2-skewed inflammation and OPN expression in nasal mucosa. CC10 administration at the sensitization phase could also reduce spleen OPN expression. The in vitro study showed that CC10 directly down-regulated the OPN expression in spleen mononuclear cells stimulated with OVA and suppressed the OPN-induced expression of Th2 cytokines and pro-inflammatory cytokines in BEAS-2B cells. Conclusion In the context of allergic airway responses, CC10 can inhibit OPN expression and suppress the Th2-promoting function of OPN, resulting in CC10's inhibitory biological effects. Cite this as: Y. Liu, X. Lu, H.-J. Yu, X.-Y. Hua, Y.-H. Cui, S.-K. Huang and Z. Liu, Clinical & Experimental Allergy, 2010 (40) 1632–1641.
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clara cell 10 kd protein suppresses chitinase 3 like 1 expression associated with eosinophilic chronic rhinosinusitis
American Journal of Respiratory and Critical Care Medicine, 2010Co-Authors: Heng Wang, Xiaobo Long, Nan Wang, Shauku HuangAbstract:Rationale: Clara cell 10-kD (CC10) protein, an antiinflammatory molecule, is involved in inflammatory upper airway diseases, but its regulatory role is unclear, particularly in the process of chronic rhinosinusitis (CRS). Objectives: To investigate the regulatory mechanisms of CC10 in eosinophilic CRS (ECRS) using an allergic mouse model. Methods: Homozygous CC10-knockout mice were used to establish an allergic ECRS model. Phenotypic changes were examined by histology, cytokine ELISA, and gene microarray analysis. Differential expression of chitinase 3-like 1 (CHI3L1) was verified by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. The functional role of CHI3L1 in vivo was assessed by the use of anti-CHI3L1 antibody in ECRS mice. CHI3L1 gene expression regulated by inflammatory cytokines and CC10 protein was performed using BEAS-2B cell line. Measurements and Main Results: Compared with wild-type mice, a significantly greater extent of inflammatory cell infiltration and tissue remodeling was found in CC10-knockout ECRS mice, which was associated with significantly higher levels of various cytokines and eotaxin-1. CHI3L1 was up-regulated in ECRS mice with a significant further increase in CC10-knockout mice. Anti-CHI3L1 treatment markedly ameliorated eosinophilic inflammation. Furthermore, nasal mucosal CC10 gene transfer in CC10-knockout mice attenuated eosinophilic inflammation and suppressed the levels of CHI3L1. Moreover, significantly up-regulated expression of CHI3L1 was noted in human ECRS. IL-1β, tumor necrosis factor–α, and IL-13 were found to up-regulate CHI3L1 expression in BEAS-2B cells, whereas CC10 inhibited such up-regulation. Conclusions: These results suggest that CHI3L1 is a novel molecule involved in ECRS and that CC10 plays a regulatory role in ECRS, presumably by attenuating CHI3L1 expression.
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infant frequent wheezing correlated to clara cell protein 10 cc10 polymorphism and concentration but not allergy sensitization in a perinatal cohort study
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: Kuender D Yang, Lichen Chen, Chia Yu Ou, Jen Chieh Chang, Rong Fu Chen, Hsiu Mei Liang, Shauku HuangAbstract:Background Wheezing episodes are common in young infants. However, the molecular mechanism of wheezing is unclear, and very few therapeutic regimens are effective. Objective This study investigated the genetic and environmental factors predisposing to infant wheezing in a birth cohort study. Methods A cohort of 1211 pregnant women was recruited for this study. Infant wheezing episodes during the first 18 months of life were correlated to parental atopic history, parental smoking, prematurity, CB IgE levels, and the sequence variant (G+38A) of the Clara cell protein 10 (CC10) gene encoding a secretary anti-inflammatory CC10 protein. Results Nine hundred eighty-three infants completed umbilical cord blood collection, and 813 infants completed the 18-month postnatal follow-up. Twenty-two percent of the infants experienced at least 1 wheezing episode, and 6.6% of the infants experienced frequent wheezing (≥3 episodes). Multivariate logistic regression showed that male sex and the CC10 G+38A polymorphism, but not prematurity, CB IgE level, passive smoking, or parental atopy, were predictors of frequent wheezing. Further studies found that infant frequent wheezing was significantly associated with the CC10 +38AA genotype and lower plasma CC10 levels at 18 months of age ( P = .046), and infants with acute wheezing episodes had significantly lower CC10 levels than those without ( P = .023). No association of wheezing episodes with allergic sensitization was observed in this cohort population. Conclusion Infant frequent wheezing is associated with the CC10 G+38A polymorphism and lower CC10 levels but not infant atopy. Clinical implications Lower CC10 expression, but not allergy sensitization, is involved in the pathogenesis of infant frequent wheezing.
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regulation of th2 responses by the pulmonary clara cell secretory 10 kd protein
The Journal of Allergy and Clinical Immunology, 2004Co-Authors: Chih Hsing Hung, Lichen Chen, Zhongjian Zhang, Allen C. Myers, Bhabadeb Chowdhury, Beverly Plunkett, Chien Ho Chen, Shauku HuangAbstract:Abstract Background Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T-cell responses remains unknown. Objective The role of CC10 in the regulation of T H 2 cytokine expression was investigated. Methods The levels of cytokine and GATA-3 expression were determined by ELISA and RT-PCR, respectively. Bronchoalveolar lavage fluid cell counts were also determined by using a standard protocol. CC10 expression in vivo was determined by immunocytochemistry and Western blotting. Results In vitro , a significant, dose-dependent suppressive effect of CC10 was found on T H 2 cytokine expression, but not IFN-γ, in splenocytes of antigen-sensitized mice. A similar suppressive effect was also noted in polarized CD4 + T H 2 cells, but not in naive CD4 + T cells. In contrast, CC10 was able to induce IFN-γ expression in naive CD4 + T cells, but not in polarized T H 1 cells. Furthermore, the suppression of T H 2 cytokine expression was concomitant with reduction of a critical transcription factor, GATA-3. Of significance was the finding that although no significant change was found in the decay kinetics of T H 2 cytokine transcripts, a significant decrease in mRNA stability of GATA-3 was seen in CC10-treated cells. In vivo , reconstitution of the CC10 gene in CC10-deficient mice resulted in significantly lower levels of T H 2 cytokines, concomitant with a decrease in GATA-3 expression, after challenge with Ag compared with those seen in mock-transduced mice, which are associated with reduced levels of pulmonary eosinophilia. Conclusion These results demonstrate, that CC10 plays a direct role in the regulation of T-cell–mediated inflammatory responses.
Tadashi Kawai - One of the best experts on this subject based on the ideXlab platform.
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serum levels of clara cell 10 kda protein are decreased in patients with asthma
Lung, 1999Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Michio Hirasawa, F Sugaya, Toshiyuki Yamada, T. Yamaguchi, Tadashi KawaiAbstract:Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (≥10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.
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serum and bal clara cell 10 kda protein cc10 levels and cc10 positive bronchiolar cells are decreased in smokers
European Respiratory Journal, 1997Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Y Shibuya, Yuji Morita, Michio Hirasawa, Ryuta Okutani, T. Yamaguchi, Tadashi KawaiAbstract:Cigarette smoking has diverse effects on the structure and function of the lung. Smoking appears to reduce the levels of Clara cell 10 kDa protein (CC10) in the alveolar lining fluid, but the influence of smoking serum on CC10 levels is still debated, and it has not been clear whether smoking reduces the number of CC10-producing lung cells. The aims of this study were to clarify the influence of smoking on CC10 levels in the alveolar lining fluid and bloodstream, and on the number of CC10-producing lung cells. CC10 concentrations were measured in sera and bronchoalveolar lavage (BAL) fluids, by means of enzyme-linked immunosorbent assay using monoclonal and polyclonal antibody, and the immunohistochemical expression of CC10 was examined in the lungs of nonsmokers and smokers using the monoclonal antibody, TY-5, against CC10/human urinary protein-1. CC10 concentrations in sera and in BAL fluids from healthy smokers were significantly lower than in healthy nonsmokers. Immunohistochemical expression of CC10 was found exclusively in nonciliated bronchiolar epithelial cells. As compared to that of nonsmokers, the mean percentage of CC10-positive bronchiolar epithelial cells was significantly decreased in lung tissue specimens obtained from smokers who had normal results in pulmonary function tests. It was concluded that smoking reduces the proportion of Clara cell 10 kDa protein-producing bronchiolar epithelial cells, resulting in decreased levels of Clara cell 10 kDa protein in the lower respiratory tract and in the bloodstream. The protein is a new blood biochemical and immunohistochemical marker, reflecting structural changes in peripheral airways induced by cigarette smoking.
Noriharu Shijubo - One of the best experts on this subject based on the ideXlab platform.
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development of an enzyme linked immunosorbent assay for clara cell 10 kda protein in pursuit of clinical significance of sera in patients with asthma and sarcoidosis
Annals of the New York Academy of Sciences, 2006Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Tetsuji Yamaguchi, Shosaku AbeAbstract:: We have produced nine monoclonal antibodies to human CC10/protein-1 and analyzed their characterization. TY-5, TY-7, and TY-8 recognized restricted possible hydrophobic epitopes and their binding to CC10 prevented the other clones from CC10 binding, suggesting that these antibodies induce strong conformational change. TY-1, TY-2, TY-3, TY-6, and 6D4 recognize amino acid residues 61–68 and the presence of disulfide bonds might be essential for epitope expression of these five clones. The best combination was TY-1 and TY-2 in developing an enzyme-linked immunosorbent assay (ELISA), whereas TY-5 was most suitable for immunohistochemistry and immunoblotting. We found significantly lower serum CC10 levels in asthmatic subjects and higher serum CC10 levels in sarcoidosis subjects than in controls. Data of CC10 levels in BAL fluids of sarcoidosis subjects were similar to those in the circulation. CC10-positive epithelial cells were significantly lower in small airways of asthmatic subjects than in controls, and CC10-positive epithelial cells were inversely correlated with T cell and mast cell accumulation in the airways of asthmatic subjects. CC10 may be a downregulator in both Th1- and Th2-mediated chronic inflammatory diseases. The use of these MoAbs and recombinant CC10 is a powerful tool to investigate the clinical roles of CC10/P1 and the structure and function of CC10/P1.
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serum levels of clara cell 10 kda protein are decreased in patients with asthma
Lung, 1999Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Michio Hirasawa, F Sugaya, Toshiyuki Yamada, T. Yamaguchi, Tadashi KawaiAbstract:Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (≥10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.
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serum and bal clara cell 10 kda protein cc10 levels and cc10 positive bronchiolar cells are decreased in smokers
European Respiratory Journal, 1997Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Y Shibuya, Yuji Morita, Michio Hirasawa, Ryuta Okutani, T. Yamaguchi, Tadashi KawaiAbstract:Cigarette smoking has diverse effects on the structure and function of the lung. Smoking appears to reduce the levels of Clara cell 10 kDa protein (CC10) in the alveolar lining fluid, but the influence of smoking serum on CC10 levels is still debated, and it has not been clear whether smoking reduces the number of CC10-producing lung cells. The aims of this study were to clarify the influence of smoking on CC10 levels in the alveolar lining fluid and bloodstream, and on the number of CC10-producing lung cells. CC10 concentrations were measured in sera and bronchoalveolar lavage (BAL) fluids, by means of enzyme-linked immunosorbent assay using monoclonal and polyclonal antibody, and the immunohistochemical expression of CC10 was examined in the lungs of nonsmokers and smokers using the monoclonal antibody, TY-5, against CC10/human urinary protein-1. CC10 concentrations in sera and in BAL fluids from healthy smokers were significantly lower than in healthy nonsmokers. Immunohistochemical expression of CC10 was found exclusively in nonciliated bronchiolar epithelial cells. As compared to that of nonsmokers, the mean percentage of CC10-positive bronchiolar epithelial cells was significantly decreased in lung tissue specimens obtained from smokers who had normal results in pulmonary function tests. It was concluded that smoking reduces the proportion of Clara cell 10 kDa protein-producing bronchiolar epithelial cells, resulting in decreased levels of Clara cell 10 kDa protein in the lower respiratory tract and in the bloodstream. The protein is a new blood biochemical and immunohistochemical marker, reflecting structural changes in peripheral airways induced by cigarette smoking.
Qin Ning - One of the best experts on this subject based on the ideXlab platform.
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Image_1_Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression.TIF
2018Co-Authors: Yang Liu, Hongwu Wang, Xiaoyang Wan, Jiaquan Huang, Weiming Yan, Xiaoping Luo, Guanxin Shen, Qin NingAbstract:Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation. Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH. Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection. Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma. However, its mechanisms of action and pathogenic roles in other disease are still unclear. In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10.Methods: A mouse FH model was established by peritoneal injection of MHV-3. The mice received CC10 protein through tail vein injection before viral infection. Survival rate, liver function, liver histology, fibrin deposition, and necrosis were examined. The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro.Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group. Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced. Furthermore, hepatic Fgl2, TNF-α, and IL-1β expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein. In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. However, there was no direct interaction between CC10 and Fgl2 as shown by co-immunoprecipitation. Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells. HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs).Conclusion:CC10 protects against MHV-3-induced FH via suppression of Fgl2 expression in macrophages. Such effects may be mediated by the transcription factor HBP1.
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Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression
Frontiers Media S.A., 2018Co-Authors: Yang Liu, Hongwu Wang, Xiaoyang Wan, Jiaquan Huang, Weiming Yan, Xiaoping Luo, Guanxin Shen, Qin NingAbstract:Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation. Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH. Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection. Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma. However, its mechanisms of action and pathogenic roles in other disease are still unclear. In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10.Methods: A mouse FH model was established by peritoneal injection of MHV-3. The mice received CC10 protein through tail vein injection before viral infection. Survival rate, liver function, liver histology, fibrin deposition, and necrosis were examined. The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro.Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group. Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced. Furthermore, hepatic Fgl2, TNF-α, and IL-1β expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein. In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. However, there was no direct interaction between CC10 and Fgl2 as shown by co-immunoprecipitation. Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells. HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs).Conclusion:CC10 protects against MHV-3-induced FH via suppression of Fgl2 expression in macrophages. Such effects may be mediated by the transcription factor HBP1
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Table_1_Clara Cell 10 kDa Protein Alleviates Murine Hepatitis Virus Strain 3-Induced Fulminant Hepatitis by Inhibiting Fibrinogen-Like Protein 2 Expression.DOC
2018Co-Authors: Yang Liu, Hongwu Wang, Xiaoyang Wan, Jiaquan Huang, Weiming Yan, Xiaoping Luo, Guanxin Shen, Qin NingAbstract:Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation. Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH. Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection. Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma. However, its mechanisms of action and pathogenic roles in other disease are still unclear. In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10.Methods: A mouse FH model was established by peritoneal injection of MHV-3. The mice received CC10 protein through tail vein injection before viral infection. Survival rate, liver function, liver histology, fibrin deposition, and necrosis were examined. The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro.Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group. Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced. Furthermore, hepatic Fgl2, TNF-α, and IL-1β expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein. In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. However, there was no direct interaction between CC10 and Fgl2 as shown by co-immunoprecipitation. Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells. HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs).Conclusion:CC10 protects against MHV-3-induced FH via suppression of Fgl2 expression in macrophages. Such effects may be mediated by the transcription factor HBP1.
Yoshihisa Itoh - One of the best experts on this subject based on the ideXlab platform.
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development of an enzyme linked immunosorbent assay for clara cell 10 kda protein in pursuit of clinical significance of sera in patients with asthma and sarcoidosis
Annals of the New York Academy of Sciences, 2006Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Tetsuji Yamaguchi, Shosaku AbeAbstract:: We have produced nine monoclonal antibodies to human CC10/protein-1 and analyzed their characterization. TY-5, TY-7, and TY-8 recognized restricted possible hydrophobic epitopes and their binding to CC10 prevented the other clones from CC10 binding, suggesting that these antibodies induce strong conformational change. TY-1, TY-2, TY-3, TY-6, and 6D4 recognize amino acid residues 61–68 and the presence of disulfide bonds might be essential for epitope expression of these five clones. The best combination was TY-1 and TY-2 in developing an enzyme-linked immunosorbent assay (ELISA), whereas TY-5 was most suitable for immunohistochemistry and immunoblotting. We found significantly lower serum CC10 levels in asthmatic subjects and higher serum CC10 levels in sarcoidosis subjects than in controls. Data of CC10 levels in BAL fluids of sarcoidosis subjects were similar to those in the circulation. CC10-positive epithelial cells were significantly lower in small airways of asthmatic subjects than in controls, and CC10-positive epithelial cells were inversely correlated with T cell and mast cell accumulation in the airways of asthmatic subjects. CC10 may be a downregulator in both Th1- and Th2-mediated chronic inflammatory diseases. The use of these MoAbs and recombinant CC10 is a powerful tool to investigate the clinical roles of CC10/P1 and the structure and function of CC10/P1.
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serum levels of clara cell 10 kda protein are decreased in patients with asthma
Lung, 1999Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Michio Hirasawa, F Sugaya, Toshiyuki Yamada, T. Yamaguchi, Tadashi KawaiAbstract:Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (≥10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.
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serum and bal clara cell 10 kda protein cc10 levels and cc10 positive bronchiolar cells are decreased in smokers
European Respiratory Journal, 1997Co-Authors: Noriharu Shijubo, Yoshihisa Itoh, Y Shibuya, Yuji Morita, Michio Hirasawa, Ryuta Okutani, T. Yamaguchi, Tadashi KawaiAbstract:Cigarette smoking has diverse effects on the structure and function of the lung. Smoking appears to reduce the levels of Clara cell 10 kDa protein (CC10) in the alveolar lining fluid, but the influence of smoking serum on CC10 levels is still debated, and it has not been clear whether smoking reduces the number of CC10-producing lung cells. The aims of this study were to clarify the influence of smoking on CC10 levels in the alveolar lining fluid and bloodstream, and on the number of CC10-producing lung cells. CC10 concentrations were measured in sera and bronchoalveolar lavage (BAL) fluids, by means of enzyme-linked immunosorbent assay using monoclonal and polyclonal antibody, and the immunohistochemical expression of CC10 was examined in the lungs of nonsmokers and smokers using the monoclonal antibody, TY-5, against CC10/human urinary protein-1. CC10 concentrations in sera and in BAL fluids from healthy smokers were significantly lower than in healthy nonsmokers. Immunohistochemical expression of CC10 was found exclusively in nonciliated bronchiolar epithelial cells. As compared to that of nonsmokers, the mean percentage of CC10-positive bronchiolar epithelial cells was significantly decreased in lung tissue specimens obtained from smokers who had normal results in pulmonary function tests. It was concluded that smoking reduces the proportion of Clara cell 10 kDa protein-producing bronchiolar epithelial cells, resulting in decreased levels of Clara cell 10 kDa protein in the lower respiratory tract and in the bloodstream. The protein is a new blood biochemical and immunohistochemical marker, reflecting structural changes in peripheral airways induced by cigarette smoking.