title: Interleukin-8: An autocrine inflammatory mediator.
abstract: Interleukin-8 (IL-8), a pro-inflammatory chemokine, induces trafficking of neutrophils across the vascular wall. The release of IL-8 is triggered by inflammatory signals from a large variety of cells. The diversity in the cellular source indicates pleiotropy of its functions. IL-8 plays a key role in host defense mechanism through its effects on neutrophil activation, but a continued presence of IL-8 in circulation in response to inflammatory conditions may lead to a variable degree of tissue damage. Like most of the peptide hormones or mediators, IL-8 transmits its signals through distinct cell surface receptors. The membrane spanning heptahelical IL-8 receptor is coupled with the effector enzyme(s) through the intermediacy of heterotrimeric GTP-binding regulatory proteins. A growing number of studies demonstrated regulation of IL-8 activity by pertussis toxin treatment, implying a role of pertussis toxin sensitive G proteins (Gi), in IL-8 induced effects. IL-8 induced activation of G-protein results in activation of phospholipase C b2 (PLCb2). This enzyme catalyzes the hydrolysis of membrane phosphoinositides to yield diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (IP3), which in turn activates protein kinase C (PKC) and mobilizes the intracellular Ca2+, respectively. Neutrophils activation of phospholipase D (PLD) and superoxide generation in response to IL-8 have also been demonstrated. Furthermore, IL-8-mediated activation of mitogen activating protein kinase (MAPK) and tyrosine phosphorylation of cellular proteins have been observed. It appears that the signalling pathways induced by IL-8 are subject to fine modulations by the demand and presence of IL-8. The presence of IL-8 in various pathophysiological condition implies that blockade of its actions could be exploited for therapeutic purposes.
authors: H.E.J. Research Institute of Chemistry, University of Karachi, Karachi, Karachi-75270, Pakistan.
authors: Atta-ur-Rahman
authors: K
authors: K
authors: Harvey
authors: R A
authors: RA
authors: Siddiqui
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D018836:Inflammation Mediators / Q000502:physiology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8