title: Double-stranded RNA induces production of RANTES and IL-8 by human nasal fibroblasts.
abstract: Double-stranded RNA (dsRNA) and the viral RNA mimic, polyinosine-polycytidylic acid (poly(I:C)), are recognized by toll-like receptor 3 (TLR3) that mediates the innate immune response to viral infections. In this study, we investigated the effects of poly(I:C) on the production of chemokines (IL-8, RANTES, and eotaxin), Type I IFNs (IFNalpha and IFNbeta), Th1-cytokines (IL-12 and IFNgamma), and pro-inflammatory cytokines (TNF-alpha and IL-1beta) by human nasal mucosa-derived fibroblasts. Human nasal fibroblasts were treated with poly(I:C), and levels of cytokines and chemokines were measured by ELISA. Incubation with poly(I:C) significantly enhanced the secretion of RANTES and IL-8. However, eotaxin, IL-1beta, TNF-alpha, IFNalpha, IFNgamma, and IL-12 were not secreted from nasal fibroblasts stimulated with poly(I:C). The JNK inhibitor SP600125 and the PI3-kinase inhibitor LY294002 significantly blocked the poly(I:C)-induced release of RANTES and IL-8, whereas the p38 MAP kinase inhibitor SB203580 suppressed poly(I:C)-induced secretion of IL-8, but not RANTES. Nasal fibroblasts play an important role in initiating antiviral responses and inflammation of the nasal cavity by producing chemokines leading to enhanced inflammatory cell recruitment.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, School of Medicine, University of Fukui, 23 Shimoaizuki, Mastuoka-cho, Yoshida-gun, Fukui 910-1193, Japan. noborut@fmsrsa.fukui-med.ac.jp
authors.forename: Noboru
authors.initials: N
authors.lastname: Takahashi
authors.forename: Takechiyo
authors.initials: T
authors.lastname: Yamada
authors.forename: Norihiko
authors.initials: N
authors.lastname: Narita
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Fujieda
mesh_terms: D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D005347:Fibroblasts / Q000276:immunology*; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology*; D010766:Phosphorylation; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D018946:Chemokine CCL5; D007369:Interferon Inducers; D016209:Interleukin-8; D012330:RNA, Double-Stranded; D051193:Toll-Like Receptors; D011070:Poly I-C