Fas inhibition attenuates lipopolysaccharide-induced apoptosis and cytokine release of rat type II alveolar epithelial cells.
The aim of this study is to investigate whether silencing of Fas could have an influence on type II alveolar epithelial cell (AEC) apoptosis and inflammatory cytokine production, which prevents alveolar healing after acute lung injury (ALI). Rat primary type II AECs were isolated by elastase cell dispersion and IgG panning. The cells were transfected with Fas-specific small interfering RNA (siRNA) followed by treatment with lipopolysaccharide (LPS), Fas ligand (FasL) or both. The effects of siRNA-mediated silencing of Fas on LPS-induced apoptosis and cytokine release were then assessed. Notably, LPS, either alone or together with FasL, significantly stimulated type II AEC apoptosis and the release of tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) (P < 0.05 versus the control without treatment). Moreover, the effects exerted by both LPS and FasL were considerably counteracted by pretreatment with Fas-siRNA (P < 0.05 versus treatment with LPS and FasL). In conclusion, inhibition of Fas can diminish LPS-induced apoptosis and inflammatory cytokine production in type II AECs, and Fas specific siRNAs may have therapeutic potentials for intervention of ALI/ARDS.
Ma
Xinhua
X
Department of ICU, Xiangya Hospital, Central South University, 410008, Changsha, China.
Xu
Daomiao
D
Ai
Yuhang
Y
Ming
Guangfeng
G
Zhao
Shuangping
S
D056809:Alveolar Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; C491898:Fas protein, rat; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor