IL-27 activates human monocytes via STAT1 and suppresses IL-10 production but the inflammatory functions of IL-27 are abrogated by TLRs and p38.
IL-27 is a member of the IL-12 family of cytokines that activates the Jak-STAT signaling pathway in a context-dependent manner and has pleiotropic effects on acquired immunity. IL-27 has the capacity to promote early stages of Th1 generation, but recent evidence has suggested a predominant suppressive effect on Th1, Th2, and Th17 differentiation. Although modest suppressive effects of IL-27 on myeloid lineage cells have been observed, there is limited knowledge about the role of IL-27 in the regulation of innate immunity. In this study we report that although in resting murine macrophages IL-27 had minimal if any effects, in resting human monocytes IL-27 had profound proinflammatory functions. IL-27 activated a STAT1-dominant pattern of signaling in human monocytes with the consequent activation of STAT1-dependent inflammatory target genes. IL-27 primed monocytes for augmented responses to TLR stimulation in a STAT1-dependent manner, altered IL-10 signaling, and attenuated IL-10-induced gene expression. Strikingly, IL-27 strongly suppressed TLR-induced IL-10 production in human monocytes. However, the proinflammatory effects of IL-27 on human monocytes were rapidly abrogated by LPS via a p38-mediated mechanism that inhibited IL-27 signaling. Our findings identify a predominantly proinflammatory function for IL-27 in human monocytes and suggest a mechanism by which the activating effects of IL-27 on innate immunity are attenuated as an immune response proceeds and IL-27 transitions to predominantly suppressive effects on acquired immunity.[1]References
- IL-27 activates human monocytes via STAT1 and suppresses IL-10 production but the inflammatory functions of IL-27 are abrogated by TLRs and p38. Kalliolias, G.D., Ivashkiv, L.B. J. Immunol. (2008) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
