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Steven M Knapp - One of the best experts on this subject based on the ideXlab platform.
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Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation
Respiratory research, 2014Co-Authors: B. Garrett Bodine, Brock G. Bennion, Emma Leatham, Felix R Jimenez, Alex J Wright, Zac R Jergensen, Connor J Erickson, Cameron M. Jones, Jeff P Johnson, Steven M KnappAbstract:Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), Interleukin 7 (IL-7), and Interleukin 14 (IL-14) in whole lung homogenates compared to controls. These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
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Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation
Respiratory Research, 2014Co-Authors: B. Garrett Bodine, Brock G. Bennion, Emma Leatham, Felix R Jimenez, Alex J Wright, Zac R Jergensen, Connor J Erickson, Cameron M. Jones, Jeff P Johnson, Steven M KnappAbstract:Background Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. Methods and results We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), Interleukin 7 (IL-7), and Interleukin 14 (IL-14) in whole lung homogenates compared to controls. Conclusions These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
Julian L. Ambrus - One of the best experts on this subject based on the ideXlab platform.
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Central role for marginal zone B cells in an animal model of Sjogren's syndrome ☆
Clinical immunology (Orlando Fla.), 2016Co-Authors: Long Shen, Chun Gao, Lakshmanan Suresh, Zhenhua Xian, Nannan Song, Lee D. Chaves, Julian L. AmbrusAbstract:Patients with Sjogren's syndrome (SS) have been shown to have abnormal B cell function and increased numbers of marginal zone B cells (MZB and MZB precursors. The current studies utilized the Interleukin 14 alpha transgenic mouse model (IL14aTG) for SS to investigate the roles of marginal zone B cells (MZB) of the innate immune system in the pathophysiology of the disease. Eliminating MZB from IL14aTG mice by B cell specific deletion of RBP-J resulted in complete elimination of all disease manifestations of SS. Mice had normal salivary gland secretions, negative autoantibodies and normal histology of the salivary and lacrimal glands compared to IL14aTG mice at the same time points. In contrast, eliminating B1 cells by deleting btk did not ameliorate the disease. Therefore, MZB are critical for the development of SS.
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IL-14 alpha, the nexus for primary Sjögren's disease in mice and humans.
Clinical immunology (Orlando Fla.), 2008Co-Authors: Long Shen, Oleh Pankewycz, Lakshmanan Suresh, Chongjie Zhang, Vijay Kumar, Julian L. AmbrusAbstract:To evaluate the role of Interleukin 14 alpha (IL-14a) in Sjogren's syndrome (SS), we evaluated the expression of IL-14a in the peripheral blood lymphocytes (PBL) of patients with primary and secondary SS and normal controls by quantitative RT-PCR. In addition, transgenic IL-14a mice were analyzed from 6 weeks of age to death for both histological and immunological features of Sjogren's disease. Patients with both primary and secondary Sjogren's syndrome expressed IL-14a at statistically higher levels in their peripheral blood compared to normal controls matched for age, sex and ethnic group. Transgenic mice in which IL-14a expression was increased constitutively were previously demonstrated to develop hypergammaglobulinemia, autoantibodies, infiltration of the parotid glands with lymphocytes, mild immune-complex mediated renal disease and large B cell lymphoma. In this paper we expand these observations to demonstrate that these mice develop all the clinical and immunological features of primary Sjogren's disease in the same relative time frame as patients with primary Sjogren's disease: stage 1-early hypergammaglobulinemia and autoantibody production, stage 2-decreased salivary gland function with early lymphocytic infiltration of the submandibular glands only, but antibody deposition in the submandibular and parotid glands, stage 3-lymphocytic infiltration of the submandibular, parotid and lacrimal glands with B and T lymphocytes and plasma cells along with interstitial lung disease and mild renal disease, and stage 4-large B cell lymphoma. Thus IL-14a is important in the pathophysiology of Sjogren's disease. The IL-14a transgenic mouse is a novel animal model that can be utilized to understand the pathophysiology of Sjogren's disease.
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Regulation of human Interleukin 14 transcription in vitro and in vivo after renal transplantation.
Transplantation, 2008Co-Authors: Nicolae Leca, M. R. Laftavi, Long Shen, Kristin Matteson, Julian L. Ambrus, Oleh PankewyczAbstract:Background. Alloantibodies and B lymphocytes are felt to contribute in increasingly important ways to the pathogenesis of both acute and chronic allograft injury. The mechanisms that lead to the formation of posttransplant alloantibodies despite immunosuppressive therapy have not been fully elucidated. Interleukin 14 (IL-14) or high molecular weight B cell growth factor secreted by activated T and B cells and follicular dendritic cells promotes B cell growth, survival and memory, and antibody production. The potential role of IL-14 in human transplantation has not been examined. Methods. Using quantitative polymerase chain reaction techniques, we examined IL-14 mRNA transcript levels in human cells and compared them to IL-2. Interleukin-14 mRNA levels were measured in isolated human T cells stimulated in vitro with mitogen and alloantigen in the presence or absence of immunosuppressive drugs. In vivo, IL-14 transcript levels were measured in peripheral blood leukocytes isolated from patients after renal transplantation. Results. In vitro, both IL-14 and IL-2 transcript levels increase after alloantigen and mitogen stimulation and are suppressed by currently used immunosuppressive agents. In vivo, IL-14 and IL-2 behave differently as IL-14 transcript levels are not reduced by immunosuppressive therapy. Interleukin-14 transcripts also increase after both immune and nonimmune injury to renal allografts. Conclusions. This is the first demonstration of human IL-14 mRNA regulation in vitro and in vivo. Given the important effects of IL-14 on B cell proliferation and antibody production, increases in IL-14 transcript levels may play a role in alloantibody formation after renal transplantation.
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Identification of B-Cell Growth Factors (Interleukin-14; High Molecular Weight-B-Cell Growth Factors) in Effusion Fluids From Patients With Aggressive B-Cell Lymphomas
Blood, 1995Co-Authors: Richard J. Ford, Archito T. Tamayo, Barbara A. Martin, Keyi Niu, Kent Claypool, Fernando Cabanillas, Julian L. AmbrusAbstract:The molecular basis of neoplastic B-cell growth is complex and poorly understood. Cytokines have been postulated to contribute to neoplastic cell growth, and many in vitro studies have confirmed this prediction, but little is known about the in vivo role of these growth factors. We have examined the production of Interleukin-14 (IL-14) (high molecular weight [HMW], B-cell growth factor [BCGF]) by aggressive intermediate (diffuse large cell) lymphomas of the B-cell type non-Hodgkin's lymphoma (NHL-B) in four patients with lymphomatous effusions. In these studies, IL-14 was detected in the effusion fluids by Western blots and IL-14 mRNA was constitutively expressed in the freshly isolated lymphoma cells that also expressed the receptor for IL-14 (IL14R). Lymphoma B cells placed at low serum and cell density proliferated in vitro to either purified IL-14 or IL-14 derived from effusion fluids. Antibodies to IL-14 removed the growth-stimulating cytokine(s) from the effusions. Cell lines developed from these patients produced IL-14 in vitro and antisense oligos to IL-14 blocked their growth in vitro. Thus, autocrine or paracrine production of IL-14 may play a significant role in the rapid proliferation of aggressive NHL-B. Interrupting this pathway could be a useful goal of therapy for patients resistant to conventional chemotherapy.
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A Potential Role for PGE and IL-14 (HMW-BCGF) in B-Cell Hyperactivity of Patients with Systemic Lupus Erythematosus.
American journal of therapeutics, 1995Co-Authors: Julian L. Ambrus, Amy Joseph, Varsha Contractor, John Long, David BlumenthalAbstract:Systemic lupus erythematosus (SLE) is a disease characterized by the prolonged production of high-affinity autoantibodies resulting in direct and immune complex-mediated tissue damage. Because autoantibody responses occur over several years, memory B cells are likely to be involved. Interleukin-14 (IL-14) is a cytokine implicated in the generation and maintenance of normal memory B cells. Many of the actions of IL-14, including inhibition of antibody synthesis and upregulation of IL-14 receptors (IL-14R), are dependent on the formation of prostaglandin E (PGE) and subsequently cAMP. We observed that IL-14 induces phospholipase A(2) (PLA(2))-dependent release of arachidonic acid from phosphatidylcholine and phosphatidylinositol. Production of PGE is blocked by the PLA(2) inhibitor bromophenacyl bromide. Exogenous PGE (misoprostol) induces similar inhibition of antibody synthesis and increases in IL-14R as IL-14. Lymphocytes from patients with inactive SLE were noted to spontaneously produce PGE. Lymphocytes from normal donors produced PGE only after Sac-activation and IL-14 stimulation. Peripheral B and T lymphocytes from SLE patients, but not normal donors, spontaneously produced IL-14. Increased numbers of peripheral B lymphocytes from patients with inactive SLE expressed IL-14R, when compared to normal donors. Thus, increased production of IL-14 and PGE in SLE may result in expansion of a memory B-cell population capable of long-term autoantibody production. Further study will be necessary to confirm these preliminary findings and to examine in greater depth the regulation of PGE and IL-14 in SLE patients and normal donors.
B. Garrett Bodine - One of the best experts on this subject based on the ideXlab platform.
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Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation
Respiratory research, 2014Co-Authors: B. Garrett Bodine, Brock G. Bennion, Emma Leatham, Felix R Jimenez, Alex J Wright, Zac R Jergensen, Connor J Erickson, Cameron M. Jones, Jeff P Johnson, Steven M KnappAbstract:Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), Interleukin 7 (IL-7), and Interleukin 14 (IL-14) in whole lung homogenates compared to controls. These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
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Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation
Respiratory Research, 2014Co-Authors: B. Garrett Bodine, Brock G. Bennion, Emma Leatham, Felix R Jimenez, Alex J Wright, Zac R Jergensen, Connor J Erickson, Cameron M. Jones, Jeff P Johnson, Steven M KnappAbstract:Background Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. Methods and results We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), Interleukin 7 (IL-7), and Interleukin 14 (IL-14) in whole lung homogenates compared to controls. Conclusions These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
Richard J. Ford - One of the best experts on this subject based on the ideXlab platform.
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Development of a Blastoid Variant, Mantle Cell Lymphoma Model in Transgenic Mice.
Blood, 2005Co-Authors: Richard J. Ford, Long Shen, Archito T. Tamayo, Chongjie Zhang, Yen-chiu Lin-lee, Stephen Brooks, John K. Cowell, Lan V. Pham, Linda C. YoshimuraAbstract:Mantle Cell Lymphoma (MCL) is a poorly understood, aggressive histotype of B-cell non-Hodgkin’s Lymphomas (NHL-B) that remains the most therapeutically resistant of the NHL-B. Little is known regarding why MCL is so clinically aggressive and therapeutically refractory. Blastoid variant MCL (MCL-BV) is an even more aggressive form of MCL that appears to be increasing in incidence in the US. It may represent progression from classic MCL, often with leukemic involvement and complex lymphoma karyotypes. Interleukin 14 (IL-14) is cytokine that was identified and cloned from a Burkitt lymphoma (BL) cell line that acts as a growth factor for normal B-lymphocytes. The expression of IL-14a protein and mRNA levels are elevated at lease fifty-fold in B-cell non-Hodgkin’s Lymphomas (NHL-B), including mantle cell lymphoma (MCL), in contrast to very low levels of IL-14a in quiescent (G o ) B cells by both western and northern blot analysis. To evaluate the role of IL-14 in vivo, we have generated transgenic mice expressing IL-14 with pEuSR. The IL-14 TG mice generally live a normal life span, however when autopsies are performed at 18 months of age, splenomegaly is noted, and 50% have evidence of B cell lymphoma. This lymphoma is CD5+, CD19+, sIgM+, CD21− and contains a monoclonal population of B-lymphocytes with rearranged immunoglobulin genes. Morphologically the lymphoma arising in IL-14 transgenic mice resembles the centroblastic/Immunoblastic histotype of DLBCL. Because of the frequent involvement of c-myc in various B cell malignancies, we crossed Eμ-myc (c-myc TG) mice with the IL-14 TG mice. By 3 months of age, 100% of the double transgenic (DTG) mice develop an aggressive B cell malignancy that is characterized by extensive lymphadenopathy and splenomegaly with intermediate to large atypical lymphoid cells, strongly resembling MCL-BV morphologically. This tumor, like that derived from the IL-14 TG mice, is CD5+, CD19+, sIgM+, CD21−. It is also CD23− and over-expresses Cyclin D1 in monoclonal B lymphoid cells with re-arranged IgH immunoglobulin genes, mimicking the MCL phenotype. At the time of autopsy, tumor infiltration of DTG mice is generally found in all organs evaluated, including peripheral blood, lymph nodes, spleen, liver, bone marrow, thymus and kidneys, consistent with the usual findings in MCL-BV. No tumors are observed in IL-14α TG or c-myc TG mice autopsied at this age. This MCL-BV model allows for the molecular and genotypic characterization of the murine B lymphoid cell compartment from birth to lymphoma development (3 mos.), including histogenesis and functional determination of the growth and survival characteristics of these tumors in DTG bone marrow and peripheral B cell populations. Preliminary comparative in vitro and in vivo (SCID Xeno-transplants) studies in DTG/MCL-BV lymphomas have shown additional molecular similarities to the pathophysiology (e.g constitutive NF-kB activation) of MCL-BV cell lines and patient samples, that should provide insights for future potential therapeutic approaches to MCL.
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Identification of B-Cell Growth Factors (Interleukin-14; High Molecular Weight-B-Cell Growth Factors) in Effusion Fluids From Patients With Aggressive B-Cell Lymphomas
Blood, 1995Co-Authors: Richard J. Ford, Archito T. Tamayo, Barbara A. Martin, Keyi Niu, Kent Claypool, Fernando Cabanillas, Julian L. AmbrusAbstract:The molecular basis of neoplastic B-cell growth is complex and poorly understood. Cytokines have been postulated to contribute to neoplastic cell growth, and many in vitro studies have confirmed this prediction, but little is known about the in vivo role of these growth factors. We have examined the production of Interleukin-14 (IL-14) (high molecular weight [HMW], B-cell growth factor [BCGF]) by aggressive intermediate (diffuse large cell) lymphomas of the B-cell type non-Hodgkin's lymphoma (NHL-B) in four patients with lymphomatous effusions. In these studies, IL-14 was detected in the effusion fluids by Western blots and IL-14 mRNA was constitutively expressed in the freshly isolated lymphoma cells that also expressed the receptor for IL-14 (IL14R). Lymphoma B cells placed at low serum and cell density proliferated in vitro to either purified IL-14 or IL-14 derived from effusion fluids. Antibodies to IL-14 removed the growth-stimulating cytokine(s) from the effusions. Cell lines developed from these patients produced IL-14 in vitro and antisense oligos to IL-14 blocked their growth in vitro. Thus, autocrine or paracrine production of IL-14 may play a significant role in the rapid proliferation of aggressive NHL-B. Interrupting this pathway could be a useful goal of therapy for patients resistant to conventional chemotherapy.
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Identification of a cDNA for a human high molecular-weight B-cell growth factor.
Proceedings of the National Academy of Sciences of the United States of America, 1993Co-Authors: Julian L. Ambrus, Kent Claypool, James Pippin, Amy Joseph, David Blumenthal, Archi Tamayo, David W. Mccourt, Anon Srikiatchatochorn, Richard J. FordAbstract:Proliferation is necessary for many of the phenotypic changes that occur during B-cell maturation. Further differentiation of mature B cells into plasma cells or memory B cells requires additional rounds of proliferation. In this manuscript, we describe a cDNA for a human B-cell growth factor we call high-molecular-weight B-cell growth factor (HMW-BCGF). Purified HMW-BCGF has been shown to induce B-cell proliferation, inhibit immunoglobulin secretion, and selectively expand certain B-cell subpopulations. Studies using antibodies to HMW-BCGF and its receptor have suggested that HMW-BCGF, while produced by T cells and some malignant B cells, acts predominantly on normal and malignant B cells. The HMW-BCGF cDNA was identified by expression cloning using a monoclonal antibody and polyclonal antisera to HMW-BCGF. Protein produced from the cDNA induced B-cell proliferation, inhibited immunoglobulin secretion, and was recognized in immunoblots by anti-HMW-BCGF antibodies. The amino acid sequence of HMW-BCGF deduced from the cDNA predicts a secreted protein of 53 kDa with three potential N-linked glycosylation sites. The identification of this cDNA will allow further studies examining physiologic roles of this cytokine. We propose to call it Interleukin 14.
Emma Leatham - One of the best experts on this subject based on the ideXlab platform.
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Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation
Respiratory research, 2014Co-Authors: B. Garrett Bodine, Brock G. Bennion, Emma Leatham, Felix R Jimenez, Alex J Wright, Zac R Jergensen, Connor J Erickson, Cameron M. Jones, Jeff P Johnson, Steven M KnappAbstract:Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), Interleukin 7 (IL-7), and Interleukin 14 (IL-14) in whole lung homogenates compared to controls. These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.
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Conditionally induced RAGE expression by proximal airway epithelial cells in transgenic mice causes lung inflammation
Respiratory Research, 2014Co-Authors: B. Garrett Bodine, Brock G. Bennion, Emma Leatham, Felix R Jimenez, Alex J Wright, Zac R Jergensen, Connor J Erickson, Cameron M. Jones, Jeff P Johnson, Steven M KnappAbstract:Background Receptors for advanced glycation end-products (RAGE) are multiligand cell-surface receptors expressed abundantly by distal pulmonary epithelium. Our lab has discovered RAGE-mediated effects in the orchestration of lung inflammation induced by tobacco smoke and environmental pollutants; however, the specific contribution of RAGE to the progression of proximal airway inflammation is still inadequately characterized. Methods and results We generated a Tet-inducible transgenic mouse that conditionally overexpressed RAGE using the club cell (Clara) secretory protein (CCSP) promoter expressed by club (Clara) cells localized to the proximal airway. RAGE was induced for 40 days from weaning (20 days of age) until sacrifice date at 60 days. Immunohistochemistry, immunoblotting, and qPCR revealed significant RAGE up-regulation when compared to non-transgenic controls; however, H&E staining revealed no detectible morphological abnormalities and apoptosis was not enhanced during the 40 days of augmentation. Freshly procured bronchoalveolar lavage fluid (BALF) from CCSP-RAGE TG mice had significantly more total leukocytes and PMNs compared to age-matched control littermates. Furthermore, CCSP-RAGE TG mice expressed significantly more tumor necrosis factor alpha (TNF-α), Interleukin 7 (IL-7), and Interleukin 14 (IL-14) in whole lung homogenates compared to controls. Conclusions These data support the concept that RAGE up-regulation specifically in lung airways may function in the progression of proximal airway inflammation.