Cell stress induced HSP are targets of regulatory T cells: A role for HSP inducing compounds as anti‐inflammatory immuno‐modulators?

Wieten, Lotte; Broere, Femke; Zee, Ruurd van der; Koerkamp, Elles klein; Wagenaar, J.A.; Eden, Willem van

doi:10.1016/j.febslet.2007.04.082

Cited by 89 publications

(62 citation statements)

References 58 publications

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“…Self-Hsp cross-reactive T cells are thought to be present at the site of inflammation and are able to enhance the production of regulatory cytokines as IL-10 and TGF-β (Hauet-Broere et al 2006;Wieten et al 2007). Another interesting finding is that, in human atopic lesional skin, expression of Hsp70 and Hsp60 is more intensive than in normal healthy skin (Ghoreishi 2000).…”

Section: Discussionmentioning

confidence: 88%

Intradermal injection of Hsp60 induces cytokine responses in canine atopic and healthy skin

Lee

Rutten

Kooten

et al. 2008

Cell Stress and Chaperones

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The purpose of this study was to investigate the immunoregulatory potential of Hsp60 in the skin of dogs with atopic dermatitis. Three dogs with chronic atopic dermatitis and four healthy dogs were injected intradermally with Hsp60 and phosphate-buffered saline. Biopsies were taken before testing from non-injected control skin, lesional and non-lesional atopic skin, and 48 and 72 h after injection. Analysis of cytokine messenger RNA was performed using quantitative real-time polymerase chain reaction. Forty-eight hours after Hsp60 injection, a rise in interleukin (IL)-10 was found (P=0.034) with the highest expression levels in non-lesional atopic and control skin. A rise of transforming growth factor beta (P=0.015) and IL12p40 (P=0.017) was noticed 72 h after Hsp60 injection in control skin. No significant differences were observed for the expression of IL-4, IL-12p35, and interferon gamma. The results indicate that Hsp60 is able to induce cytokines of a regulatory and Th1 phenotype in the skin. Furthermore, this study seems to provide a first indication of deficient Hsp60 response in atopic dermatitis affected skin.

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Section: Discussionmentioning

confidence: 88%

Intradermal injection of Hsp60 induces cytokine responses in canine atopic and healthy skin

Lee

Rutten

Kooten

et al. 2008

Cell Stress and Chaperones

Self Cite

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“…Hsp70 is a protein with powerful immunological properties: it has been associated with the innate immune response (Triantafilou et al 2008), and a strong binding to B cells, which are responsible for antibody production, has been shown (Asea 2005). Although there are several studies that link immunity to Hsp70 in the promotion of chronic inflammatory conditions such as multiple sclerosis, diabetes, and cardiovascular disease, many other studies show that such immune response attenuates inflammatory disease (Wieten et al 2007). Specifically, it has been shown that patients with stable and unstable angina (Herz et al 2006) and with acute coronary syndrome (Zhang et al 2010) have lower levels of anti-Hsp70 antibodies than the healthy population and that microvascular and macrovascular complications in patients with type 1 diabetes positively correlate with lower levels of anti-Hsp70 and anti-Hsp60 antibodies (Gruden et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Extracellular heat shock protein 70 (HSPA1A) and classical vascular risk factors in a general population

Dulín

García‐Barreno

Guisasola

2010

Cell Stress and Chaperones

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Atherosclerosis is a chronic inflammatory and autoimmune disease. Candidate molecules/autoantigens include heat shock proteins (HSPs); Hsp70 (HSPA1A) is one of the best studied HSPs. Various studies have shown a correlation between extracellular Hsp70 (eHsp70) and anti-Hsp70/anti-Hsp60 antibody concentration and development of atherosclerosis. A random sample of 456 people aged 40-60 (218 males, 234 females) was studied to investigate the prevalence of traditional vascular risk factors and eHsp70 and antiHsp70/anti-Hsp60 antibodies levels, according to the risk of vascular disease. Task Force Chart was applied for classification. Subjects were divided into three groups: G0 (with no vascular risk factor or a risk lower than 5%), n=239; G1 (moderated 10-20% risk, who do not have established disease) n=161; and G2 (established atherosclerosis disease) n=52. eHsp70 and anti-Hsp70 were significantly lower in the atherosclerosis group (group 2) with respect to the other groups. Disease-free people showed the highest anti-Hsp60 concentration compared with the other two groups. A correlation has not been demonstrated between the concentrations of circulating Hsp70 (HSPA1A), anti-Hsp70, and antiHsp60 and classical vascular risk factors and C-reactive protein. Low levels of eHsp70 and anti-Hsp70 antibodies should be considered as candidate FRV. Simultaneous decrease of eHsp70 and anti-Hsp70 antibodies would be explained by circulating immune complex formation, and both could be proposed as biomarkers for the progression of atherosclerotic disease. Levels of circulating anti-Hsp60 antibodies may constitute a marker of inflammation in atherosclerosis.

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“…36,37,42,43 HSP90 has been implicated in studies investigating similar autoimmune diseases and it has been reported that T cells respond to extracellular HSP90 by increasing their anti-inflammatory cytokines. 44 Other recent work has shown that T-cell activation by the T-cell receptor is dependent on functioning HSP90. 45 Despite findings suggesting a role for HSP90 in SLE, or the antiinflammatory effects of HSP90 inhibition, little has been published exploring the effect of HSP90 inhibition in SLE.…”

Section: Introductionmentioning

confidence: 97%

Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus

et al. 2012

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Elevated expression of heat shock protein 90 (HSP90) has been found in kidneys and serum of systemic lupus erythematosus (SLE) patients and MRL/Mp-Fas lpr /Fas lpr (MRL/lpr) autoimmune mice. We investigated if inhibition of HSP90 would reduce disease in MRL/ lpr mice. In vitro, pretreatment of mesangial cells with HSP90 inhibitor Geldanamycin prior to immune-stimulation showed reduced expression of IL-6, IL-12 and NO. In vivo, we found HSP90 expression was elevated in MRL/lpr kidneys when compared to C57BL/6 mice and MRL/lpr mice treated with HSP90 inhibitor 17-DMAG. MRL/lpr mice treated with 17-DMAG showed decreased proteinuria and reduced serum anti-dsDNA antibody production. Glomerulonephritis and glomerular IgG and C3 were not significantly affected by administration of 17-DMAG in MRL/lpr. 17-DMAG increased CD8 1 T cells, reduced double-negative T cells, decreased the CD4/CD8 ratio and reduced follicular B cells. These studies suggest that HSP90 may play a role in regulating T-cell differentiation and activation and that HSP90 inhibition may reduce inflammation in lupus.

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Cell stress induced HSP are targets of regulatory T cells: A role for HSP inducing compounds as anti‐inflammatory immuno‐modulators?

Cited by 89 publications

References 58 publications

Intradermal injection of Hsp60 induces cytokine responses in canine atopic and healthy skin

Intradermal injection of Hsp60 induces cytokine responses in canine atopic and healthy skin

Extracellular heat shock protein 70 (HSPA1A) and classical vascular risk factors in a general population

Heat shock protein 90 inhibition by 17-DMAG lessens disease in the MRL/lpr mouse model of systemic lupus erythematosus

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