المؤلفون: Kathryn A Niese, Marc E. Rothenberg, Nives Zimmermann, Lesley G. Ellies, Monica G. Chiaramonte

المصدر: Respiratory Research, Vol 11, Iss 1, p 87 (2010)
Respiratory Research
Niese, Kathryn A; Chiaramonte, Monica G; Ellies, Lesley G; Rothenberg, Marc E; & Zimmermann, Nives. (2010). The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis. Respiratory Research, 11(1), 87. doi: http://dx.doi.org/10.1186/1465-9921-11-87Test. Retrieved from: http://www.escholarship.org/uc/item/08r3r3gmTest

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Arginine, Ovalbumin, Pulmonary Fibrosis, Inflammation, Mice, Transgenic, Biology, 03 medical and health sciences, chemistry.chemical_compound, Bleomycin, Mice, 0302 clinical medicine, Pulmonary fibrosis, medicine, Animals, Amino acid transporter, RNA, Messenger, Lung, Interleukin 4, 030304 developmental biology, Mice, Knockout, lcsh:RC705-779, 0303 health sciences, Arginine transport, Arginase, Macrophages, Research, lcsh:Diseases of the respiratory system, Ornithine, respiratory system, medicine.disease, Molecular biology, Asthma, 3. Good health, respiratory tract diseases, Up-Regulation, Mice, Inbred C57BL, Disease Models, Animal, chemistry, Amino Acid Transport Systems, Basic, Cytokines, Collagen, Interleukin-4, medicine.symptom, Inflammation Mediators, STAT6 Transcription Factor, 030215 immunology

الوصف: Background Arginine is an amino acid that serves as a substrate for the enzymes nitric oxide synthase (NOS) and arginase, leading to synthesis of NO and ornithine, respectively. As such, arginine has the potential to influence diverse fundamental processes in the lung. Methods We used mice deficient in cationic amino acid transporter (CAT) 2 in models of allergic airway inflammation and pulmonary fibrosis. Results We report that the arginine transport protein CAT2 was over-expressed in the lung during the induction of allergic airway inflammation. Furthermore, CAT2 mRNA was strongly induced by transgenically over-expressed IL-4, and allergen-induced expression was dependent upon signal-transducer-and-activator-of-transcription (STAT) 6. In situ mRNA hybridization demonstrated marked staining of CAT2, predominantly in scattered mononuclear cells. Analysis of allergic airway inflammation and bleomycin-induced inflammation in CAT2-deficient mice revealed that while inflammation was independent of CAT2 expression, bleomycin-induced fibrosis was dependent upon CAT2. Mechanistic analysis revealed that arginase activity in macrophages was partly dependent on CAT2. Conclusion Taken together, these results identify CAT2 as a regulator of fibrotic responses in the lung.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff488e09613d0836ca395abf78fca43bTest
http://respiratory-research.com/content/11/1/87Test

المؤلفون: Barry J. Moynihan, Sophie Laberge, Pascale Ferraro, Marie-Claire Michoud, James G. Martin, Barbara Tolloczko, Souad El Bassam

المصدر: Respiratory Research
Respiratory Research, Vol 9, Iss 1, p 84 (2008)

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Eotaxin, Chemokine CCL11, Receptor complex, Receptor expression, medicine.medical_treatment, Myocytes, Smooth Muscle, Suppressor of Cytokine Signaling Proteins, Biology, 03 medical and health sciences, chemistry.chemical_compound, Interferon-gamma, 0302 clinical medicine, Suppressor of Cytokine Signaling 1 Protein, Downregulation and upregulation, medicine, Humans, RNA, Messenger, Lung, Interleukin 4, Cells, Cultured, 030304 developmental biology, Cell Proliferation, lcsh:RC705-779, 0303 health sciences, Interleukin-13, Research, lcsh:Diseases of the respiratory system, Molecular biology, Interleukin-13 Receptor alpha1 Subunit, 3. Good health, Receptors, Interleukin-4, Cytokine, chemistry, Suppressor of Cytokine Signaling 3 Protein, Interleukin 13, Interleukin-13 Receptor alpha2 Subunit, Calcium, Interleukin-4, STAT6 Transcription Factor, Histamine, 030215 immunology

الوصف: BackgroundIL-13 is a critical mediator of allergic asthma and associated airway hyperresponsiveness. IL-13 acts through a receptor complex comprised of IL-13Rα1 and IL-4Rα subunits with subsequent activation of signal transducer and activator of transcription 6 (STAT6). The IL-13Rα2 receptor may act as a decoy receptor. In human airway smooth muscle (HASM) cells, IL-13 enhances cellular proliferation, calcium responses to agonists and induces eotaxin production. We investigated the effects of pre-treatment with IL-4, IL-13 and IFN-γ on the responses of HASM cells to IL-13.MethodsCultured HASM were examined for expression of IL-13 receptor subunits using polymerase chain reaction, immunofluorescence microscopy and flow cytometry. Effects of cytokine pre-treatment on IL-13-induced cell responses were assessed by looking at STAT6 phosphorylation using Western blot, eotaxin secretion and calcium responses to histamine.ResultsIL-13Rα1, IL-4Rα and IL-13Rα2 subunits were expressed on HASM cells. IL-13 induced phosphorylation of STAT6 which reached a maximum by 30 minutes. Pre-treatment with IL-4, IL-13 and, to a lesser degree, IFN-γ reduced peak STAT6 phosphorylation in response to IL-13. IL-13, but not IFN-γ, pre-treatment abrogated IL-13-induced eotaxin secretion. Pre-treatment with IL-4 or IL-13 abrogated IL-13-induced augmentation of the calcium transient evoked by histamine. Cytokine pre-treatment did not affect expression of IL-13Rα1 and IL-4Rα but increased expression of IL-13Rα2. An anti-IL-13Rα2 neutralizing antibody did not prevent the cytokine pre-treatment effects on STAT6 phosphorylation. Cytokine pre-treatment increased SOCS-1, but not SOCS-3, mRNA expression which was not associated with significant increases in protein expression.ConclusionPre-treatment with IL-4 and IL-13, but not IFN-γ, induced desensitization of the HASM cells to IL-13 as measured by eotaxin secretion and calcium transients to histamine. The mechanism of IL-4 and IL-13 induced desensitization does not appear to involve either downregulation of receptor expression or induction of the IL-13Rα2 or the SOCS proteins.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2c81423398c6fa937cad6dea21c893dTest
https://pubmed.ncbi.nlm.nih.gov/19116009Test

المؤلفون: Alexa Pham, David H. Broide, Ajit Varki, Peter Rosenthal, Dae Jae Song, Jae Youn Cho, Shanna Dayan, Marina Miller, Taylor A. Doherty

المصدر: Respiratory Research
Respiratory Research, Vol 11, Iss 1, p 154 (2010)
Cho, Jae Youn; Song, Dae Jae; Pham, Alexa; Rosenthal, Peter; Miller, Marina; Dayan, Shanna; et al.(2010). Chronic OVA allergen challenged Siglec-F deficient mice have increased mucus, remodeling, and epithelial Siglec-F ligands which are up-regulated by IL-4 and IL-13.. Respiratory Research, 11(1), 154. doi: http://dx.doi.org/10.1186/1465-9921-11-154Test. Retrieved from: http://www.escholarship.org/uc/item/2jz1d9rgTest

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Ovalbumin, Antigens, Differentiation, Myelomonocytic, Inflammation, Ligands, 03 medical and health sciences, Mice, 0302 clinical medicine, Fibrosis, Internal medicine, medicine, Animals, Lung, Interleukin 4, Cells, Cultured, 030304 developmental biology, lcsh:RC705-779, Sialic Acid Binding Immunoglobulin-like Lectins, 0303 health sciences, Interleukin-13, biology, Research, Epithelial Cells, lcsh:Diseases of the respiratory system, respiratory system, medicine.disease, Mucus, Up-Regulation, Fibronectin, Eosinophils, Mice, Inbred C57BL, Endocrinology, 13. Climate action, Immunology, Interleukin 13, biology.protein, Respiratory epithelium, Airway Remodeling, Interleukin-4, medicine.symptom, 030215 immunology

الوصف: Background In this study we examined the role of Siglec-F, a receptor highly expressed on eosinophils, in contributing to mucus expression, airway remodeling, and Siglec-F ligand expression utilizing Siglec-F deficient mice exposed to chronic allergen challenge. Methods Wild type (WT) and Siglec-F deficient mice were sensitized and challenged chronically with OVA for one month. Levels of airway inflammation (eosinophils), Siglec-F ligand expresion and remodeling (mucus, fibrosis, smooth muscle thickness, extracellular matrix protein deposition) were assessed in lung sections by image analysis and immunohistology. Airway hyperreactivity to methacholine was assessed in intubated and ventilated mice. Results Siglec-F deficient mice challenged with OVA for one month had significantly increased numbers of BAL and peribronchial eosinophils compared to WT mice which was associated with a significant increase in mucus expression as assessed by the number of periodic acid Schiff positive airway epithelial cells. In addition, OVA challenged Siglec-F deficient mice had significantly increased levels of peribronchial fibrosis (total lung collagen, area of peribronchial trichrome staining), as well as increased numbers of peribronchial TGF-β1+ cells, and increased levels of expression of the extracellular matrix protein fibronectin compared to OVA challenged WT mice. Lung sections immunostained with a Siglec-Fc to detect Siglec-F ligand expression demonstrated higher levels of expression of the Siglec-F ligand in the peribronchial region in OVA challenged Siglec-F deficient mice compared to WT mice. WT and Siglec-F deficient mice challenged intranasally with IL-4 or IL-13 had significantly increased levels of airway epithelial Siglec-F ligand expression, whereas this was not observed in WT or Siglec-F deficient mice challenged with TNF-α. There was a significant increase in the thickness of the peribronchial smooth muscle layer in OVA challenged Siglec-F deficient mice, but this was not associated with significant increased airway hyperreactivity compared to WT mice. Conclusions Overall, this study demonstrates an important role for Siglec-F in modulating levels of chronic eosinophilic airway inflammation, peribronchial fibrosis, thickness of the smooth muscle layer, mucus expression, fibronectin, and levels of peribronchial Siglec-F ligands suggesting that Siglec-F may normally function to limit levels of chronic eosinophilic inflammation and remodeling. In addition, IL-4 and IL-13 are important regulators of Siglec-F ligand expression by airway epithelium.

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الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c99154e77a98dc9c6a9b80bffda163c7Test