Interleukin-6: a regulator of plasma protein gene expression in hepatic and non-hepatic tissues.
The cytokine which is now called interleukin-6 (IL-6) has emerged as a major systemic alarm signal produced by essentially every injured tissue in response to almost every kind of damage. The hallmark of IL-6 gene regulation is its induction in many different tissues by inflammation-associated cytokines, bacterial products, virus infection and by activation of any of the three major signal transduction pathways (diacylglycerol, cAMP and Ca2(+)-activated). Many of these inducers act largely through a 23 base-pair "multi-response element" in the IL-6 promoter. Different tissues secrete multiple post-translationally modified forms of IL-6 (six protein species in the size range 23 to 30 kDa, and additional forms of size greater than or equal to 45 kDa). IL-6 plays a key role in activating a variety of host defence mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiological and immunological status of the host (e.g. the "acute phase" plasma protein response). IL-6 enhances plasma protein gene expression not only in hepatocytes but also in monocytes, fibroblasts and lymphocytes. Elevated levels of IL-6 are observed in body fluids during acute and chronic infections, neoplasia and autoimmune diseases. The nature of the IL-6 receptor in hepatic and non-hepatic cells, the different signal transduction pathways involved in the regulation of particular liver genes by IL-6, the association between IL-6 levels in body fluids and clinical outcome and between IL-6 haplotypes and specific disease states remain to be explored in detail.
Rockefeller University, New York, NY 10021.
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Sehgal
D000818:Animals; D001483:Base Sequence; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008969:Molecular Sequence Data
D001798:Blood Proteins; D015850:Interleukin-6