The macrophage response towards LPS and its control through the p38(MAPK)-STAT3 axis

Cellular Signalling
Johannes G BodeDieter Häussinger

Abstract

In macrophages detection of gram-negative bacteria particularly involves binding of the outer-wall component lipopolysaccharide (LPS) to its cognate receptor complex, comprising Toll like receptor 4 (TLR4), CD14 and MD2. LPS-induced formation of the LPS receptor complex elicits a signaling network, including intra-cellular signal-transduction directly activated by the TLR4 receptor complex as well as successional induction of indirect autocrine and paracrine signaling events. All these different pathways are integrated into the macrophage response towards an inflammatory stimulus by a highly complex cross-talk of the pathways engaged. This also includes a tight control by several intra- and inter-cellular feedback loops warranting an inflammatory response sufficient to battle invading pathogens and to avoid non-essential tissue damage caused by an overwhelming inflammatory response. Several evidences indicate that the reciprocal cross-talk between the p38(MAPK)-pathway and signal transducer and activator of transcription (STAT)3-mediated signal-transduction forms a critical axis successively activated by LPS. The balanced activation of this axis is essential for both induction and propagation of the inflammatory macrophage resp...Continue Reading

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