Arginase 1 contributes to fibrogenesis in the lungs of silica-challenge mice

Introduction: Arginase 1 (ARG1) is considered as an important contributor for fibrosis and can be released from alternatively activated macrophages (M2) by IL13-dependent mechanism. IL-13 was shown to be implicated in murine silicosis (Ferreira et al., J. Immunol., 191:5220, 2013). Aim: In this study we investigated the potential contribution of ARG1 in fibrosis and granuloma formation in an experimental model of silicosis in mice. Methods: Anesthetized male Swiss-Webster mice received intranasal instillation of silica particles (10 mg) or saline. Analyzes were made 28 days post-silica and included:i) lung function, ii) morphological and morphometric evaluation and iii) ARG1 and F4/80 labelling.Administration of ARG1 inhibitor Nor-NOHA (1 mg/kg, p.o.) was made for 5 consecutive days, starting 23 days post-silica challenge. Results: Mice responded to silica with increased basal levels of lung resistance and elastance, as well as with hyper-reactivity to methacholine. A marked response of fibrosis and granuloma formation, in parallel to an increased labelling for ARG1 and F4/80, was also detected in the lungs of mice. Treatment with Nor-NOHA restored lung function and reduced granuloma area (5.5% ± 0.7%)(mean ± SEM; p Conclusion: Our data show that Nor-NOHA restored lung function and suppressed granuloma formation in silica-challenge mice, suggesting that ARG1 seems to contribute to fibrogenesis in silicosis. Additional experiments are needed in order to investigate the presence of M2 macrophages in the lung tissue of silicotic mice. Financial support: FIOCRUZ, FAPERJ, CNPq (Brazil).