Differential expression of stress proteins in human adult astrocytes in response to cytokines

Various lines of evidence suggest a close relationship between heat shock p roteins (hsp) and several autoimmune diseases such as arthritis, diabetes a nd multiple sclerosis. While enhanced expression of hsp in autoimmune disea ses is often regarded as a non-specific bystander effect of the inflammator y process, surprisingly little is known on hsp regulation by inflammatory m ediators such as cytokines. In this study cytokine-induced expression of hs p60, hsp27 and alpha B-crystallin was studied in cultures of primary human adult astrocytes at the mRNA as well as at the protein level. We show diffe rential hsp expression patterns in response to pro-inflammatory and immunor egulatory cytokines. Hsp60 expression was found to be enhanced in response to cytokines as diverse as IL-1 beta, TNF-alpha, IL-4, IL-6 and IL-10. Upre gulation of hsp27, however, was primarily induced by immunoregulatory cytok ines like IL-4, IL-6 and TGF-beta whereas alpha B-crystallin expression was found to be enhanced by the pro-inflammatory cytokine TNF-alpha only. None of the cytokines studied was able to enhance expression of all three hsp s imultaneously. These results show that in human astrocytes induced expressi on of hsp27 and alpha B-crystallin is dependent on the presence of a define d set of stimuli, while induced expression of hsp60 is a much less selectiv e event. This highly differential pattern of hsp expression in response to inflammatory mediators known to play an important role in the pathogenesis of autoimmune diseases indicates that hsp responses are specific rather tha n non-specific bystander responses. (C) 2000 Elsevier Science B.V. All righ ts reserved.