PloS one, 2011-08, Vol.6 (8), p.e23185-e23185
2011
Details
- Autor(en) / Beteiligte
- Titel
- IL-1 and IL-23 mediate early IL-17A production in pulmonary inflammation leading to late fibrosis
- Ist Teil von
- PloS one, 2011-08, Vol.6 (8), p.e23185-e23185
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Idiopathic pulmonary fibrosis is a devastating as yet untreatable disease. We demonstrated recently the predominant role of the NLRP3 inflammasome activation and IL-1β expression in the establishment of pulmonary inflammation and fibrosis in mice. The contribution of IL-23 or IL-17 in pulmonary inflammation and fibrosis was assessed using the bleomycin model in deficient mice. We show that bleomycin or IL-1β-induced lung injury leads to increased expression of early IL-23p19, and IL-17A or IL-17F expression. Early IL-23p19 and IL-17A, but not IL-17F, and IL-17RA signaling are required for inflammatory response to BLM as shown with gene deficient mice or mice treated with neutralizing antibodies. Using FACS analysis, we show a very early IL-17A and IL-17F expression by RORγt(+) γδ T cells and to a lesser extent by CD4αβ(+) T cells, but not by iNKT cells, 24 hrs after BLM administration. Moreover, IL-23p19 and IL-17A expressions or IL-17RA signaling are necessary to pulmonary TGF-β1 production, collagen deposition and evolution to fibrosis. Our findings demonstrate the existence of an early IL-1β-IL-23-IL-17A axis leading to pulmonary inflammation and fibrosis and identify innate IL-23 and IL-17A as interesting drug targets for IL-1β driven lung pathology.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0023185Titel-ID: cdi_plos_journals_1307351321
- Format
- –
- Schlagworte
- Analysis, Animals, Antibodies, Bacterial infections, Biology, Bleomycin, Bleomycin - administration & dosage, Bone morphogenetic proteins, Chronic obstructive pulmonary disease, Collagen, Cytokines, Drug dosages, E coli, Enzyme-Linked Immunosorbent Assay, Escherichia coli, Female, Fibrosis, Flow Cytometry, Homeostasis, Human health and pathology, Hépatology and Gastroenterology, Infections, Infectious diseases, Inflammasomes, Inflammation, Inflammatory response, Interleukin 1, Interleukin 17, Interleukin 23, Interleukin-17 - genetics, Interleukin-17 - metabolism, Interleukin-1beta, Interleukin-1beta - administration & dosage, Interleukin-1beta - genetics, Interleukin-1beta - metabolism, Interleukin-23 - genetics, Interleukin-23 - metabolism, Interleukin-23 Subunit p19, Interleukin-23 Subunit p19 - genetics, Interleukin-23 Subunit p19 - metabolism, Laboratories, Life Sciences, Lung, Lung - drug effects, Lung - metabolism, Lung - pathology, Lung diseases, Lung Injury, Lung Injury - etiology, Lung Injury - metabolism, Lymphocytes, Lymphocytes T, Male, Medical research, Medicine, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Neutrophils, Pneumonia, Pneumonia - genetics, Pneumonia - metabolism, Pneumonia - pathology, Pulmonary Fibrosis, Pulmonary Fibrosis - genetics, Pulmonary Fibrosis - metabolism, Pulmonary Fibrosis - pathology, Reverse Transcriptase Polymerase Chain Reaction, Rheumatoid arthritis, Rodents, Signaling, T cells, T-Lymphocyte Subsets, T-Lymphocyte Subsets - drug effects, T-Lymphocyte Subsets - metabolism, Transforming Growth Factor beta1, Transforming Growth Factor beta1 - metabolism, Transforming growth factor-b1, Transforming growth factors, Traumatic brain injury, Wound healing