Mechanisms of Action of the Resistin-like Molecule (RELM)-β) in Asthmatic Airways Remodelling

Abstract

RATIONALE: We have addressed the possible role of RELM-β in asthmatic airways remodelling. We hypothesized that 1) Expression of RELM-β is elevated in airways of asthmatics compared with controls; 2) The remodelling Th2-cytokine IL-13 increases RELM-β expression in airways epithelium in vitro and 3) RELM-β acts on fibroblasts to induce production of extracellular matrix protein. METHODS: ELISA was employed to measure concentrations of RELM-β in bronchoalveolar lavage fluid (BAL) and the serum obtained from asthmatics and controls (n = 10 for each group). The effects of IL-13 on the expression RELM-β in primary cultured airway epithelial cells was determined by ELISA and RT-PCR. Western blot and RT-PCR were used to evaluate the effects of RELM-β on the expression of extracellular matrix proteins and TGF-β2 in human lung fibroblast cells (MRC5) and primary cultured airway fibroblast cells. RESULTS: The mean concentration of RELM-β was elevated in BAL fluid but not serum of asthmatic patients compared to controls. IL-13 significantly enhanced RELM-β expression in primary cultured airway epithelial cells. RELM-β increased the expression of collagen I, but not collagen III in airway fibroblast cells at both the mRNA and protein levels (p < 0.01). Additionally, RELM-β increased TGF-β2 mRNA expression (p < 0.05). CONCLUSIONS: Our data suggest that IL-13 might contribute to increased expression of RELM-β in asthmatic airways which may in turn contribute to airways remodelling by induction of TGF-β2 and collagen I expression.