| Author |
Yamamoto, Nobuyuki Matsunaga, Kazuto Kanai, Kuninobu Minakata, Yoshiaki Hiramatsu, Masataka Akamatsu, Keiichiro Nakanishi, Masanori Kawabata, Hiroki Ichinose, Masakazu Morishita, Yukiko Sugiura, Hisatoshi Hirano, Tsunahiko Kikuchi, Takashi Oka, Asako Ichikawa, Tomohiro Koarai, Akira |
| Description |
Author Affiliation: Ichikawa T ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Sugiura H ( Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.); Koarai A ( Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.); Minakata Y ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Kikuchi T ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Morishita Y ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Oka A ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Kanai K ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Kawabata H ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Hiramatsu M ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Akamatsu K ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Hirano T ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Nakanishi M ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Matsunaga K ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Yamamoto N ( Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama 641-8509, Japan); Ichinose M ( Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan.) |
| Abstract |
Viral infection often triggers asthma exacerbation and contributes to airway remodeling. Cell signaling in viral infection is mainly mediated through TLR3. Many mediators are involved in airway remodeling, but matrix metalloproteinases (MMPs) are key players in this process in asthma. However, the role of TLR3 activation in production of MMPs is unknown. In this study, we examined the effects of polyinosinic-polycytidylic acid [poly(I:C)], a ligand for TLR3, on production of MMPs in human lung fibroblasts, with a focus on nitrosative stress in TLR3 modulation of MMP production. After lung fibroblasts were treated with poly(I:C), production of MMP-1, -2, and -9 and inducible NO synthase (iNOS) was assessed. The roles of NF-κB and IFN regulatory factor-3 (IRF-3) in the poly(I:C)-mediated production of MMPs and the responsiveness to poly(I:C) of normal lung fibroblasts and asthmatic lung fibroblasts were also investigated. Poly(I:C) augmented production of MMPs and iNOS in fibroblasts, and an iNOS inhibitor diminished this production of MMPs. Poly(I:C) stimulated translocation of NF-κB and IRF-3 into the nucleus in fibroblasts and inhibition of NF-κB or IRF-3 abrogated the poly(I:C)-induced increase in both iNOS expression and release of MMPs. Poly(I:C)-induced production of iNOS and MMPs was greater in asthmatic fibroblasts than in normal fibroblasts. We conclude that viral infection may induce nitrosative stress and subsequent MMP production via NF-κB- and IRF-3-dependent pathways, thus potentiating viral-induced airway remodeling in asthmatic airways. |
