Cytokines induce stress protein formation in cultured cardiac myocytes

Löw-Friedrich, Iris; Weisensee, Dirk; Mitrou, Paris S.; Schoeppe, W.

doi:10.1007/bf00795385

Cited by 52 publications

(22 citation statements)

References 23 publications

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“…In human monocytes, LPS and TNF␣ lead to the increased expression of hsp70 (33). A similar induction of hsp70 by cytokines has been reported in nonimmune cells such as rat pancreatic islets and cardiac myocytes (34,35). This adds to more direct evidence indicating that hsp70, as other hsp, is involved in antigen presentation and mediates the induction of T helper 1-type cytokines in immune cells thus increasing cellular immunity (36,37).…”

Section: Overexpression Of Hsp70supporting

confidence: 68%

p38-dependent Enhancement of Cytokine-induced Nitric-oxide Synthase Gene Expression by Heat Shock Protein 70

Bellmann¹,

Burkart²,

Bruckhoff³

et al. 2000

Journal of Biological Chemistry

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Heat shock protein (hsp) 70 protects cells against stress by means of its ability to chaperone denatured proteins and to modulate stress-activated signaling pathways. Because inflammatory processes are often accompanied by hsp expression and because stress and cytokines share several signaling pathways, we investigated the possibility that hsp70 might modulate the cellular response to cytokines. We found that stable cell clones overexpressing hsp70, or cells shortly after transfection with hsp70, produced 2 times more nitric oxide and inducible nitric-oxide synthase (iNOS) protein and mRNA in response to cytokines than control cells expressing undetectable amounts of hsp70. Since mitogenactivated protein kinases participate in the activation of iNOS by cytokines, we investigated whether hsp70 affected the activation of these signaling pathways. hsp70 overexpression led to a specific enhancement of the activation of the p38 pathway by cytokines, producing little or no effect on the activation of extracellular signal-regulated kinase or Jun N-terminal kinase. Blocking p38 activity with SB203580 totally abolished the enhancing effect of hsp70 on cytokine-induced endogenous iNOS mRNA accumulation or transcription of an iNOS promoter-driven luciferase gene, while having little effect on the cytokine response observed in control cells. We conclude that the p38 pathway acts as an enhancing factor in the activation of iNOS by cytokines and that hsp70 can modulate the cellular response to cytokines by acting on signaling elements upstream of p38.

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Section: Overexpression Of Hsp70supporting

confidence: 68%

p38-dependent Enhancement of Cytokine-induced Nitric-oxide Synthase Gene Expression by Heat Shock Protein 70

Bellmann¹,

Burkart²,

Bruckhoff³

et al. 2000

Journal of Biological Chemistry

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“…Induction of BiP expression, which is primarily due to transcriptional activation (36), may be brought about by a number of cellular stress mechanisms including ischemia and/or reperfusion injury (37), glucose starvation (36), failure of glycosylation or malfolding of proteins (38,39), heat stress (38), cytokines (40), oxidative stress, and depletion of intracellular Ca 2ϩ stores. There is evidence that up-regulation of BiP may be involved in the immune response to tumors or during allograft rejection.…”

Section: Discussionmentioning

confidence: 99%

The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis

Corrigall

Bodman‐Smith

Fife

et al. 2001

The Journal of Immunology

165

137

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Rheumatoid arthritis (RA) is the most common, crippling human autoimmune disease. Using Western blotting and tandem mass spectroscopy, we have identified the endoplasmic reticulum chaperone BiP, a 78-kDa glucose-regulated protein, as a possible autoantigen. It preferentially stimulated increased proliferation of synovial T cells from patients with RA but not from patients with other arthritides. Mice with established collagen- or pristane-induced arthritis developed IgG Abs to BiP. Although BiP injected in CFA failed to induce arthritis in several strains of rats and mice, including HLA-DR4+/−- and HLA-DR1+/+-transgenic animals, it completely inhibited the development of arthritis when given i.v. 1 wk before the injection of type II collagen arthritis. Preimmunization with BiP suppressed the development of adjuvant arthritis in Lewis rats in a similar manner. This is the first report of a mammalian chaperone that is an autoantigen in human RA and in experimental arthritis and that can also prevent the induction of experimental arthritis. These findings may stimulate the development of new immunotherapies for the treatment of RA.

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“…Human atherosclerotic plaques express a spectrum of inflammatory cytokines, including interferon-␥, interleukin-1␣ and -1␤, and tumor necrosis factor-␣, 33,34 all of which have been shown to increase heat shock protein expression in a range of cell types. [35][36][37][38][39] Alternatively, the localized expression of heat shock proteins may promote the production of cytokines, the enhanced expression of adhesion molecules, and the establishment and propagation of the inflammatory response. A number of studies lend support to this proposition.…”

Section: Discussionmentioning

confidence: 99%

Circulating Heat Shock Protein 60 Is Associated With Early Cardiovascular Disease

et al. 2000

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Abstract-The phylogenetically conserved nature of heat shock proteins (Hsp) has led to the proposition that they may provide a link between infection and the inflammatory component to vascular disease. Hypertension is associated with atherosclerosis. Here, we measured circulating heat shock protein and heat shock protein antibody levels in association with borderline hypertension. Seventy-two men with borderline hypertension patients and 75 normotensive control subjects (diastolic blood pressure 85 to 94 and Ͻ80 mm Hg, respectively) were selected from a population-screening program. The levels of Hsp60; Hsp70; and anti-human Hsp60, anti-human Hsp70, and anti-mycobacterial Hsp65 antibodies were determined with enzyme immunoassay. The presence of carotid atherosclerosis and the intima-media thickness values were determined with ultrasonography. A major novel observation in this report was the detection of circulating Hsp60, which was present at a significantly enhanced level in patients with borderline hypertension. Furthermore, serum Hsp60 was associated with intima-media thicknesses (PϽ0.01). Anti-Hsp65 antibody levels were higher in borderline hypertension (PϽ0.001), whereas Hsp70 and anti-Hsp70 antibody levels did not differ. In contrast to anti-Hsp65 antibody, anti-Hsp60 antibody levels were lower in borderline hypertension (PϽ0.03), although the difference was quantitatively small. None of the parameters evaluated were associated with atherosclerosis, metabolic factors, or smoking. We identified elevated Hsp60 levels in patients with borderline hypertension and an association between early atherosclerosis and Hsp60 levels. The physiological role of Hsp60 release has yet to be defined, but given the proinflammatory properties, these proteins could be involved in the induction/progression of both hypertension and atherosclerosis, as well as being markers for early cardiovascular disease. (Hypertension. 2000;36:303-307.)

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Cytokines induce stress protein formation in cultured cardiac myocytes

Cited by 52 publications

References 23 publications

p38-dependent Enhancement of Cytokine-induced Nitric-oxide Synthase Gene Expression by Heat Shock Protein 70

p38-dependent Enhancement of Cytokine-induced Nitric-oxide Synthase Gene Expression by Heat Shock Protein 70

The Human Endoplasmic Reticulum Molecular Chaperone BiP Is an Autoantigen for Rheumatoid Arthritis and Prevents the Induction of Experimental Arthritis

Circulating Heat Shock Protein 60 Is Associated With Early Cardiovascular Disease

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