IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages

Speaker: 吳岳穎

Commentator: 葉才明  老師

Time: 9/24/2003 13:00~14:00

Place: Room 601

Abstract:

The growth, immunity, differentiation and hematopoiesis are controlled by the coordinated action of the cytokine network. As cytokines interact with receptors on the cell surface, they activate intracellular signaling through tyrosine kinases, Janus kinases (JAK), and transcription factors, signal transducers and activators of transcription (STATs). The activated STAT proteins translocate into the nucleus and induce the transcription of a range of cytokine responsive genes. IL-6, which activates STAT3, is a multifunctional cytokine that regulates inflammatory responses, hematopoiesis and acute phase response; accordingly, over-production of IL-6 is associated with immune-mediated diseases, such as rheumatoid arthritis and Crohn disease. In contrast, anti-inflammatory cytokine IL-10, which also activates STAT3, could balance the effects of IL-6. What accounts for such distinct functions of these two cytokines is still unknown. Several members of the suppressor of cytokine signaling (SOCS) protein family are cytokine-inducible proteins that act in a classical negative-feedback loop to attenuate cytokine signal transduction. Among these, SOCS3 is strongly expressed by LPS, IL-6, and IL-10 stimulation in macrophages. However, SOCS3 has higher affinity to IL-6 receptor subunit, gp130, than to IL-10 receptor. In this study, the authors used the Cre-loxP system to generate mice lacking SOCS3 in macrophages and neutrophils. They found that similar to IL-10, IL-6 could sustain the activation of STAT3 and suppress the LPS-induced production of TNF in Socs3^-/- macrophages. Thus, SOCS3 is a central negative regulator of IL-6 signaling in macrophages. According to that, inhibition of SOCS3 activity in macrophages represents a potential strategy by which to treat IL-6-mediated inflammatory diseases.

References:

1.      Chen, X.P. et al. SOCS: physiological suppressors of cytokine signaling. J. Cell Sci. 113, 2813-2819 (2000).

2.      Yasukawa, H. et al. IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat. Immunol. 4, 551-556 (2003)