Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells
Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells
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DOI:
10.2500/ajr.2008.22.3136
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发表时间:
2008-03-01
期刊:
影响因子:
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通讯作者:
Lane, Andrew P.
中科院分区:
文献类型:
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作者:
Ramanathan, Murugappan, Jr.;Lee, Won-Kyung;Lane, Andrew P.
Background: Chronic rhinosinusitis with nasal polyps (CRS omega NPs) is a disorder characterized by persistent eosirtophilic Th2 inflammation and frequent sinonasal microbial colonization. It has been postulated that an abnormal mucosal immune response underlies disease pathogenesis. The relationship between Th2 inflammatory cytokines and the innate immune function of sinonasal epithelial cells (SNECs) has not been explored.Methods: Human SNECs (HSNECs) isolated front control subjects and patients with CRS were assessed for expression of antimicrobial innate immune genes and proinflanimatory cytokine genes by real-time polymerase chain reaction, ELISA, and flow cytometry. A model of the Th2 inflammatory environment was created by exposure of primary HSNEC to the Th2 cytokine interleukin (IL)-4 or IL-13 for 36 hours, with subsequent assessment of innate immune gene expression.Results: HSNEC obtained front CRSwNP patients displayed decreased expression of mnltiple antimicrobial innate immune markers, including toll-like receptor 9, human beta-defensin 2, and surfactant protein A. Baseline expression of these genes by normal and CRS HSNEC in culture is significantly down-regulated after incubation with IL-4 or IL-13.Conclusion: Expression of multiple innate immune genes by HSNEC is reduced in CRSwNP. One mechanism appears to be a direct effect of the leukocyte-derived Th2 cytokines present in the sinonasal mucosa in CRSwNP. Impaired mucosal innate immunity may contribute to microbial colonization and abnormal immune responses associated with CRSwNP.