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Caihong Zhu - One of the best experts on this subject based on the ideXlab platform.

  • NFKB1 mediates th1 th17 activation in the pathogenesis of psoriasis
    Cellular Immunology, 2018
    Co-Authors: Fusheng Zhou, Zhengwei Zhu, Jinping Gao, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu
    Abstract:

    Abstract This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

  • NFKB1 mediates Th1/Th17 activation in the pathogenesis of psoriasis
    Cellular immunology, 2018
    Co-Authors: Fusheng Zhou, Zhengwei Zhu, Jinping Gao, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu
    Abstract:

    Abstract This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

Fusheng Zhou - One of the best experts on this subject based on the ideXlab platform.

  • NFKB1 mediates th1 th17 activation in the pathogenesis of psoriasis
    Cellular Immunology, 2018
    Co-Authors: Fusheng Zhou, Zhengwei Zhu, Jinping Gao, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu
    Abstract:

    Abstract This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

  • NFKB1 mediates Th1/Th17 activation in the pathogenesis of psoriasis
    Cellular immunology, 2018
    Co-Authors: Fusheng Zhou, Zhengwei Zhu, Jinping Gao, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu
    Abstract:

    Abstract This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

Michael D. Burkitt - One of the best experts on this subject based on the ideXlab platform.

  • Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration.
    Cell Death and Disease, 2017
    Co-Authors: Michael D. Burkitt, Rachael Hough, Tristan Townsend, Jonathan M. Williams, D. Mark Pritchard
    Abstract:

    Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. NFKB1−/− mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2−/− mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), NFKB1−/−, Nfkb2−/− and c-Rel−/− mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and NFKB1−/− mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in NFKB1−/− mice than in WT mice. NFKB1−/− mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of NFKB1−/− mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of NFKB1−/− mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of NFKB1−/− mice to DNA damage.

  • Su1973 Tamoxifen Induced Gastric Atrophy Is Regulated by the NF-κB Subunit NFKB1
    Gastroenterology, 2015
    Co-Authors: Jonathan M. Williams, D. Mark Pritchard, Jorge Caamaño, Rosalind Norman, Joseph M. Tang, Carrie A. Duckworth, Michael D. Burkitt
    Abstract:

    Introduction Chronic Helicobacter felis infection of C57BL/6 mice results in gastric corpus atrophy. We have previously demonstrated that the outcome of H. felis infection is altered by deletion of specific NF-κB subunits. NFKB1 -/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection, whereas, Nfkb2 -/- mice were protected. The oestrogen receptor antagonist tamoxifen (TAM) has recently been shown to cause acute, reversible gastric atrophy in mice. In wild-type mice, this is associated with an increase in proliferating epithelial cells. We therefore hypothesised that gastric atrophy and altered epithelial cell turnover induced by TAM may be regulated by signalling involving NF-κB subunits. Method Groups of 5 adult female C57BL/6 (WT), NFKB1 -/- , Nfkb2 -/- and c-Rel -/- mice were administered 150 mg/kg TAM by IP injection. Animals were culled 72 h later and the gastric corpus underwent quantitative histological assessment. Gastric atrophy was quantified using a validated visual analogue score. Cell positional scoring was used to quantify H + /K + ATPase expressing cells and Ki67 positive cells; gastric epithelial cells expressing cleaved-caspase 3 were quantified in 10 high-powered fields (hpf) per mouse. Results Morphological scoring demonstrated that TAM induced gastric atrophy in WT mice (median composite atrophy score (MCAS) 2 vs 0 in untreated WT mice, p + /K + ATPase or active caspase 3 positive cells was however seen. Nfkb2 -/- and c -Rel -/- mice exhibited similar phenotypes to WT mice. TAM treated NFKB1 -/- mice developed more severe gastric atrophy with marked antralisation of the corpus epithelium (MCAS 4 vs 1 in untreated NFKB1 -/- mice, p NFKB1 -/- mice also exhibited corpus gland elongation after TAM treatment (36.1 ± 0.9 vs 23.9 ± 1.2cph, p 2.5 fold reduction in the number of parietal cells compared with untreated NFKB1 -/- mice (p 2.3 fold increase in proliferating cells (p NFKB1 -/- mice. Conclusion NFKB1 mediated signalling influences the severity of gastric mucosal atrophy and cell proliferation following TAM administration. This correlates closely with our previous observations following H. felis infection. As NFKB1 signalling plays a similar role in two models of gastric atrophy, this suggests that it may have a generic role in regulating the development of this pathology. Disclosure of interest None Declared.

  • 606 NFKB1 deficiency alters susceptibility to helicobacter spp induced il 1β secretion in bone marrow derived dendritic cells
    Gastroenterology, 2015
    Co-Authors: Joseph M. Tang, Jorge Caamaño, Carrie A. Duckworth, D M Pritchard, Michael D. Burkitt
    Abstract:

    Introduction Deletion of specific NF-κB subunits in mice alters the outcome of Helicobacter felis infection. NFKB1 -/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection, whereas Nfkb2 -/- mice were protected from this pathology. The mechanisms underlying these outcomes remain unclear, but gastric Il1b transcript abundance was increased in H. felis infected NFKB1 -/- mice relative to WT, and polymorphisms at the IL1B locus have also been associated with gastric cancer in humans. Il1b transcription is regulated by classical pathway NF-κB signalling. IL-1β secretion also requires the formation of inflammasome complexes, which form following intracellular pathogen recognition, and lead to the autocatalysis of pro-caspase 1 and subsequent cleavage of IL-1β. We hypothesised that inflammasome signalling was altered in mice with abrogated NF-κB signalling and that this influenced H. felis induced pathology. We therefore investigated inflammasome mediated signalling in bone marrow derived dendritic cells (BMDCs) from mice lacking specific NF-κB subunits. Method Cells were harvested from C57BL/6, NFKB1 -/- , Nfkb2 -/- and c-Rel -/- bone marrow. Dendritic cells were differentiation using 20 ng/ml GM-CSF for 7 days. BMDCs and WT derived gastric epithelial organoids were primed with 20 ng/ml LPS and exposed to 300 μg/ml silica, 5 mM ATP, H. pylori (ATCC 53726) or H. felis (ATCC 49179) (MOI 1:100) with or without a pan-caspase inhibitor (Z-VAD-fmk), an inhibitor of NADPH oxidase (APDC) or 50 mM KCl. Secreted IL-1β and TNF concentrations were measured by ELISA. Results LPS alone induced TNF, but not Il-1β, secretion in all genotypes of BMDCs. Both silica and ATP induced IL-1β secretion in WT BMDCs pre-stimulated with LPS (750 ± 65 and 530 ± 77 pg/ml). BMDCs derived from NF-κB deficient mice secreted similar amounts of Il-1β in response to these stimuli. Inflammasome inhibitors returned IL-1β secretion to unstimulated levels. Gastric epithelial organoid cultures treated with LPS and silica did not secrete either IL-1β or TNF. Following exposure to H. felis or H. pylori , NFKB1 -/- BMDCs, but not other genotypes, exhibited a 2.6 fold increase in IL-1β secretion compared to untreated cells or cells stimulated with LPS. This was abrogated by Z-VAD-fmk. Conclusion These data identify potent inflammasome activation in NF-κB deficient BMDCs. H. pylori and H. felis also weakly stimulated inflammasome activation in NFKB1-/- BMDCs. This mechanism may contribute to the more severe gastric phenotype that is observed in NFKB1 -/- mice in vivo following H. felis infection. Further studies are required to identify how NF-κB1 deletion influences inflammasome formation, and whether altered IL-1β transcription is involved. Disclosure of interest None Declared.

  • NF-κB1, NF-κB2 and c-Rel differentially regulate susceptibility to colitis-associated adenoma development in C57BL/6 mice.
    The Journal of Pathology, 2015
    Co-Authors: Michael D. Burkitt, Joseph M. Tang, Carrie A. Duckworth, A Hanedi, Lorraine A. O'reilly, Tracy L Putoczki, Jonathan M. Williams, Rod Dimaline, Steve Gerondakis, Jorge Caamaño
    Abstract:

    NF-κB signalling is an important factor in the development of inflammation-associated cancers. Mouse models of Helicobacter-induced gastric cancer and colitis-associated colorectal cancer have demonstrated that classical NF-κB signalling is an important regulator of these processes. In the stomach, it has also been demonstrated that signalling involving specific NF-κB proteins, including NF-κB1/p50, NF-κB2/p52, and c-Rel, differentially regulate the development of gastric pre-neoplasia. To investigate the effect of NF-κB subunit loss on colitis-associated carcinogenesis, we administered azoxymethane followed by pulsed dextran sodium sulphate to C57BL/6, NFKB1−/−, Nfkb2−/−, and c-Rel−/−mice. Animals lacking the c-Rel subunit were more susceptible to colitis-associated cancer than wild-type mice, developing 3.5 times more colonic polyps per animal than wild-type mice. Nfkb2−/− mice were resistant to colitis-associated cancer, developing fewer polyps per colon than wild-type mice (median 1 compared to 4). To investigate the mechanisms underlying these trends, azoxymethane and dextran sodium sulphate were administered separately to mice of each genotype. Nfkb2−/− mice developed fewer clinical signs of colitis and exhibited less severe colitis and an attenuated cytokine response compared with all other groups following DSS administration. Azoxymethane administration did not fully suppress colonic epithelial mitosis in c-Rel−/− mice and less colonic epithelial apoptosis was also observed in this genotype compared to wild-type counterparts. These observations demonstrate different functions of specific NF-κB subunits in this model of colitis-associated carcinogenesis. NF-κB2/p52 is necessary for the development of colitis, whilst c-Rel-mediated signalling regulates colonic epithelial cell turnover following DNA damage. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  • Effect of Helicobacter felis infection and somatic deletion of NFκB family members on the murine gastric microbiome
    The Lancet, 2014
    Co-Authors: Michael D. Burkitt, Sarah L. Burgess, D. Mark Pritchard
    Abstract:

    Abstract Background The development of gastric atrophy in C57BL/6 mice infected with Helicobacter felis is differentially regulated by signalling involving NFκB1 and NFκB2. After infection, more severe atrophy develops in NFKB1-/- mice than in wild-type (wt) mice, whereas Nfkb2-/- mice are protected from atrophic gastritis. In addition, the development of pathological changes induced by Helicobacter pylori is delayed in INS-Gas mice maintained in germ-free conditons compared with those in conventional animal house conditions. Inflammasome-deficient mice have altered immunological responses that can lead to development of a dominant dysbiosis, which is sufficient to alter the outcome of dextran sodium sulphate induced colitis. We hypothesised that the different phenotypes observed in H felis infected mice lacking specific NFκB proteins could be influenced by altered gastric microbiota. We have therefore quantified the abundance of specific bacterial phyla in NFKB1-/-, Nfkb2-/-, and C57BL/6 mice with and without H felis infection. Methods We used C57BL/6, NFKB1-/-, and Nfkb2-/- mice aged 6 weeks. Three mice of each type were infected with H felis by gavage, humanely killed at 12 weeks, and gastric antral DNA extracted. Total bacterial load and relative abundance of α-proteobacteria, γ-proteobacteria, Bacteriodetes, Firmicutes, and Actinobacteria were measured by quantitative PCR (qPCR) of 16S rDNA. Colonisation by H felis was assessed with qPCR for FlaA; samples were normalised to murine Gapdh. Findings Untreated wt mice had 3·4 times and 2·6 times greater universal bacterial transcripts than did NFKB1-/- and Nfkb2-/- mice, respectively. Actinobacteria abundance was 6·0 times greater in untreated NFKB1-/- mice and 7·0 times greater in Nfkb2-/- mice than in wt mice. α-proteobacteria were 9·0 times more abundant in untreated NFKB1-/- mice than in wt mice. H felis infection of wt mice resulted in increases of 5·6 times and 16·7 times in α-proteobacteria and γ-proteobacteria, respectively, compared with uninfected mice. γ-proteobacteria were more abundant in all infected groups, but significantly more so in Nfkb2-/- mice than in others (p H felis (phylum γ-Proteobacteria) in infected Nfkb2-/- than in wt mice. Infected Nfkb2-/- mice also had a 3·3-times greater abundance of actinobacteria than did infected wt mice. No statistically significant differences were observed in the abundance of Firmicutes or Bacteroidetes. Interpretation The constitution of the murine gastric antral microbiome is affected both by H felis infection and by somatic deletion of NFκB family members. Since deletion of NFκB1 and NFκB2 alter susceptibility to H felis induced gastric atrophy, our data support the hypothesis that specific differences in microbiota could cause or signal this altered susceptibility. Further studies are needed to determine whether specific organisms influence the development of gastric disease either individually or within complex communities. Funding Wellcome Trust.

Denang Zeng - One of the best experts on this subject based on the ideXlab platform.

  • Insertion/deletion polymorphism in the promoter region of NFKB1 gene increases susceptibility for superficial bladder cancer in Chinese.
    DNA and cell biology, 2010
    Co-Authors: Tielong Tang, Shu Cui, Xian-zhong Deng, Zhiyong Gong, Guo Jiang, Pingxi Wang, Bo Liao, Zhonghai Fei, Shuyan Xian, Denang Zeng
    Abstract:

    Recently, a functional insertion/deletion polymorphism (−94 insertion/deletion ATTG) in the promoter of NFKB1 gene, which encodes the p50 subunit of nuclear factor-κB protein complex, was identified. The aim of this study was to explore the association between this polymorphism and bladder cancer in a Chinese population. The NFKB1 polymorphism was assessed in 207 patients with superficial transitional cell carcinomas in bladder and in 228 age-, sex-, and smoking-matched healthy volunteers. The polymerase chain reaction assay was used to determine the NFKB1 genotypes. Genomic DNA used for the assay was extracted from peripheral blood lymphocytes. This study found that the frequency of ATTG2 allele in bladder cancer patients was significantly higher than that in control subjects (65.2% vs. 56.1%, p = 0.006, odds ratio = 1.465), suggesting that the functional NFKB1 promoter polymorphism is associated with increased risk for superficial transitional cell carcinoma of the bladder.

  • insertion deletion polymorphism in the promoter region of NFKB1 gene increases susceptibility for superficial bladder cancer in chinese
    DNA and Cell Biology, 2010
    Co-Authors: Tielong Tang, Shu Cui, Xian-zhong Deng, Zhiyong Gong, Guo Jiang, Pingxi Wang, Bo Liao, Zhonghai Fei, Shuyan Xian, Denang Zeng
    Abstract:

    Recently, a functional insertion/deletion polymorphism (−94 insertion/deletion ATTG) in the promoter of NFKB1 gene, which encodes the p50 subunit of nuclear factor-κB protein complex, was identified. The aim of this study was to explore the association between this polymorphism and bladder cancer in a Chinese population. The NFKB1 polymorphism was assessed in 207 patients with superficial transitional cell carcinomas in bladder and in 228 age-, sex-, and smoking-matched healthy volunteers. The polymerase chain reaction assay was used to determine the NFKB1 genotypes. Genomic DNA used for the assay was extracted from peripheral blood lymphocytes. This study found that the frequency of ATTG2 allele in bladder cancer patients was significantly higher than that in control subjects (65.2% vs. 56.1%, p = 0.006, odds ratio = 1.465), suggesting that the functional NFKB1 promoter polymorphism is associated with increased risk for superficial transitional cell carcinoma of the bladder.

Xiaodong Zheng - One of the best experts on this subject based on the ideXlab platform.

  • NFKB1 mediates th1 th17 activation in the pathogenesis of psoriasis
    Cellular Immunology, 2018
    Co-Authors: Fusheng Zhou, Zhengwei Zhu, Jinping Gao, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu
    Abstract:

    Abstract This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.

  • NFKB1 mediates Th1/Th17 activation in the pathogenesis of psoriasis
    Cellular immunology, 2018
    Co-Authors: Fusheng Zhou, Zhengwei Zhu, Jinping Gao, Chao Yang, Leilei Wen, Lu Liu, Xianbo Zuo, Xiaodong Zheng, Yinjuan Shi, Caihong Zhu
    Abstract:

    Abstract This study was aimed to investigate whether NFKB1 participates in the pathogenesis of psoriasis by mediating Th1/Th17 cells. In this study, expression of NFKB1 was assessed in skin tissues from psoriasis patients and the healthy controls through Western blot and Immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum levels of IFN-γ, IL-17 (IL-17A) and IL-17RA. The imiquimod-induced psoriasis mouse model was employed to examine the role of NFKB1 in psoriasis via the assessment of psoriasis area and severity index (PASI), including erythema, thickness and scales. The effects of NFKB1 on Th1/Th17 cells in were examined by flow cytometry. In vitro co-culture of Th1/Th17 cells isolated from different mice with HaCat cells was conducted to elucidate the effect of Th1/Th17 cells-mediated by NFKB1 on HaCat cells by MTT, wound healing and transwell invasion assay, respectively. The results showed that NF-κB p105/p50 expression in skin tissues was significantly increased in psoriasis (n = 21) compared to the healthy controls (n = 16), as well as levels of serum INF-γ and IL-17. Additionally, NF-κB p105/p50 expression in lesional skin tissues was much higher than that in non-lesional skin tissues of the same patients. In the psoriasis mouse model, NFKB1 overexpression significantly elevated the scores of erythema, thickness and scales. Besides, NFKB1 up-regulated the level of NF-κB p105/p50, INF-γ, T-bet, IL-17 and RORγt, as well as Th1/Th17 cells in skin tissues of psoriasis mice. Finally, in vitro assay confirmed that the activation of Th1 and Th17 mediated by NFKB1 in psoriasis promoted the proliferation, migration and invasion of keratinocytes. These findings suggest a critical role for NFKB1 in the regulation of Th1 and Th17 in psoriasis.