Abstract
Cytokines play pivotal roles not only in normal cellular functions, but also in the pathogenesis of many diseases, such as acute lung injury (ALI). Epithelia cells in the lung are important for controlling the production of inflammatory mediators, which are critical to the pathogenesis of ALI. Understanding of positive/negative regulation of cytokine signaling may provide new therapeutic targets. SOCS proteins have been identified as feedback inhibitors of cytokine‐induced JAK/STAT signaling. However, the role of SOCS‐1/‐3 proteins in the regulation of cytokine production in lung epithelial cells is unclear. In this study, using lung epithelial cell lines we test whether SOCS‐1 or ‐3 contributes to the inhibition of cytokine production. Our initial results show that IFNγ, TNFα and LPS (to a less extent) induced SOCS‐1/‐3 gene and protein expression as well as production of IL‐6 and MCP‐1. To test whether SOCS proteins inhibit IL‐6 or MCP‐1 production, cells were transfected with siRNA of SOCS‐1 or −3, stimulated with IFNγ or TNFα, and IL‐6/MCP‐1release was measured. The data shows that silencing of SOCS‐1 expression increased MCP‐1 production as expected. However, SOCS‐3 gene knock down had no effects on MCP‐1/IL‐6 production. Together, these results indicate that SOCS‐1 and ‐3 differentially regulate MCP‐1/IL‐6 production in lung epithelial cells. (Shock‐Novo Nordisk Fellowship)
Published Version
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