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

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Author: Bajramović, J.J. · Bsibsi, M. · Geutskens, S.B. · Hassankhan, R. · Verhulst, K.C. · Stege, G.J.J. · Groot, C.J.A. de · Noort, J.M. van
Institution: TNO Preventie en Gezondheid
Source:Journal of Neuroimmunology, 1-2, 106, 14-22
Identifier: 235602
doi: doi:10.1016/S0165-5728(99)00260-X
Keywords: Health · Astrocytes · Heat shock proteins · Human · Multiple sclerosis · Heat shock protein · Heat shock protein 27 · Heat shock protein 60 · Interleukin 10 · Interleukin 1beta · Interleukin 4 · Interleukin 6 · Messenger RNA · Tumor necrosis factor alpha · Adult · Autoimmune disease · Human cell · Immunoregulation · Inflammation · Protein expression · Adjuvants, Immunologic · Aged · Aged, 80 and over · Astrocytes · Cells, Cultured · Chaperonin 60 · Crystallins · Cytokines · Female · Heat-Shock Proteins · Humans · Inflammation Mediators · Male · Middle Aged · RNA, Messenger · Up-Regulation


Various lines of evidence suggest a close relationship between heat shock proteins (hsp) and several autoimmune diseases such as arthritis, diabetes and multiple sclerosis. While enhanced expression of hsp in autoimmune diseases is often regarded as a non-specific bystander effect of the inflammatory process, surprisingly little is known on hsp regulation by inflammatory mediators such as cytokines. In this study cytokine-induced expression of hsp60, hsp27 and αB-crystallin was studied in cultures of primary human adult astrocytes at the mRNA as well as at the protein level. We show differential hsp expression patterns in response to pro-inflammatory and immunoregulatory cytokines. Hsp60 expression was found to be enhanced in response to cytokines as diverse as IL-1β, TNF-α, IL-4, IL-6 and IL-10. Upregulation of hsp27, however, was primarily induced by immunoregulatory cytokines like IL-4, IL-6 and TGF-β whereas αB-crystallin expression was found to be enhanced by the pro-inflammatory cytokine TNF-α only. None of the cytokines studied was able to enhance expression of all three hsp simultaneously. These results show that in human astrocytes induced expression of hsp27 and αB-crystallin is dependent on the presence of a defined set of stimuli, while induced expression of hsp60 is a much less selective 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 than non-specific bystander responses. (C) 2000 Elsevier Science B.V. Chemicals/CAS: Adjuvants, Immunologic; Chaperonin 60; Crystallins; Cytokines; Heat-Shock Proteins; Inflammation Mediators; RNA, Messenger