Abstract

Introduction: The pathogenesis of silicosis has been related to the accumulation of inflammatory cells that produce fibrogenic and inflammatory cytokines and growth factors. Although silicosis has been studied intensely, little is known about the crucial cellular mechanisms that initiate and drive the process of inflammation and fibrogenesis. Since FIZZ1 has direct action on myofibroblasts and is involved in the fibrotic process, it is intended, study the role of this molecule and their signaling pathway in silicosis.

Methods: Fifteen male mice C57Bl/6, aged 6 weeks-old with 20-25g, was divided into two groups. The control group (CTRL, n=6), received 50µl of sterile saline by intratracheal (i.t.) route. Silica group (SIL, n=9), received 20mg of silica crystals in 50µl of saline by i.t. route. The lungs were removed for histology, immunohistochemistry and morphometric analysis. All the experimental procedures were performed according to the guidelines of the internal ethical commission of animals (868/1523 FMUSP,Brazil).

Results: We found a significant increase of FIZZ1 in SIL group (12.19± 1.65) compared with CTRL group (1.94±0.540), P<0.009. In addition, SIL group showed significant increase of a-SMA (25.99±2.80) and CD163 (15.23±2.16) when compared with CTRL group (8.88±3.10; 6.37±2.98, respectively).

Conclusions: Instillation of silica in mice results in pathological changes that mimic the pattern of human silicosis. Our preliminary data show, for the first time, the participation of FIZZ1 signaling pathway in Silicosis model. Also, we found a M2 macrophage response in SIL group. Indeed, more studies are necessary to elicited the mechanisms that drive the silicosis process.