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001-es BibID:BIBFORM041840
Első szerző:Murai, Hiroki
Cím:Alternaria-Induced Release of IL-18 from Damaged Airway Epithelial Cells : n NF-kB Dependent Mechanism of Th2 Differentiation? / Hiroki Murai, Huibin Qi, Barun Choudhury, Jim Wild, Nilesh Dharajiya, Swapnil Vaidya, Anjana Kalita, Attila Bacsi, David Corry, Alexander Kurosky, Allan Brasier, Istvan Boldogh, Sanjiv Sur
Dátum:2012
Megjegyzések:BACKGROUND: A series of epidemiologic studies have identified the fungus Alternaria as a major risk factor for asthma. The airway epithelium plays a critical role in the pathogenesis of allergic asthma. These reports suggest that activated airway epithelial cells can produce cytokines such as IL-25, TSLP and IL-33 that induce Th2 phenotype. However the epithelium-derived products that mediate the pro-asthma effects of Alternaria are not well characterized. We hypothesized that exposure of the airway epithelium to Alternaria releasing cytokines that can induce Th2 differentiation.METHODOLOGY/PRINCIPAL FINDING: We used ELISA to measure human and mouse cytokines. Alternaria extract (ALT-E) induced rapid release of IL-18, but not IL-4, IL-9, IL-13, IL-25, IL-33, or TSLP from cultured normal human bronchial epithelial cells; and in the BAL fluids of naïve mice after challenge with ALT-E. Both microscopic and FACS indicated that this release was associated with necrosis of epithelial cells. ALT-E induced much greater IL-18 release compared to 19 major outdoor allergens. Culture of naïve CD4 cells with rmIL-18 induced Th2 differentiation in the absence of IL-4 and STAT6, and this effect was abrogated by disrupting NF- ?B p50 or with a NEMO binding peptide inhibitor.CONCLUSION/SIGNIFICANCE: Rapid and specific release of IL-18 from Alternaria-exposed damaged airway epithelial cells can directly initiate Th2 differentiation of naïve CD4(+) T-cells via a unique NF-?B dependent pathway.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:PLoS One. - 7 : 2 (2012), p. e30280. -
További szerzők:Qi, Huibin Choudhury, Barun K. Wild, Jim Dharajiya, Nilesh G. Vaidya, Swapnil Kalita, Anjana Bácsi Attila (1967-) (immunológus) Corry, David Kurosky, Alexander Brasier, Allan R. Boldogh István Sur, Sanjiv
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