Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
+44 1223 790975
ISSN: 2155-9899
+44 1223 790975
Ahmadreza Jamshidi
Accepted Abstracts: J Clin Cell Immunol
S ilica is a core part of the cause of Coal Workers? Pneumoconiosis (CWP), which is a chronic occupational lung disease characterized by irreversible pulmonary fibrosis. However, the underlying immunologic mechanisms of CWP are poorly understood. Macrophages constitute the first line of cellular defense against pathogens. Autophagy is a fundamental cellular homeostasis pathway that operates with the intracellular degradation/recycling system. In response to invading pathogens, induction of the autophagic process in macrophages constitutes a crucial mechanism in innate immunity. Here, it is demonstrated that microRNA 21 (miR-21), an elevated miRNA in silica-induced pulmonary fibrosis, is one of the main players in silica- cytotoxicity. Silica-cytotoxicity in RAW264.7 cells measured by cytotoxic cell survival assays was closely associated with the expression of miR-21. P62, indicator for autophagic degradation, increased in a dose/time-dependent way in cultured RAW264.7 cells due to silica exposure. Blocking miR-21 with anti-miR-21 led to a decreased expression of p62 in 200 μg/ml silica-treated RAW264.7 cells for 12 hours and the suppression of phosphor-Akt (ser473) was as well observed. In a cell cycle analysis, a significant increased arrest in the G1/G0 phase by anti-miR-21 was found at 48 hours after silica-treatment. Notably, obtained results demonstrated that anti-miR-21 raised factors involved in autophagosome formation. Moreover, augmented autophagy by anti-miR-21 resulted in an increase in the apoptotic population after silica exposure. The findings show that miR- 21 is a crucial molecule for alleviating silica-induced cell death in RAW264.7 cells by inhibiting the PI3K/AKT pathway and enhancing autophagy, providing a new insight into the mechanisms of CWP.