In-vitro effects of Mycobacterium bovis BCG-lysate and its derived heat shock proteins on cytokines secretion by blood mononuclear cells of rheumatoid arthritis patients in comparison with healthy controls

Sheikhi, Abdolkarim; Nazarian, Morteza; Khadem-al-melleh, Alireza; Nasab, Nouraddin Mousavi; Esmaeilzadeh, Abdolreza; Yahaghi, Nasrin; Sheikhi, Razieh

doi:10.1016/j.intimp.2008.01.034

Cited by 12 publications

(10 citation statements)

References 32 publications

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“…Therefore, the presence of HSP-reactive T cells is not an exclusive finding in RA, and the positive proliferative response of peripheral blood mononuclear cells (PBMC) to human HSP60 has been shown to be unrelated to RA activity and severity 68 . Moreover, recent studies have suggested that both bacterial and human HSPs might be suppressive in RA through the induction of regulatory T cells and the deviation of the cytokine response to T helper 2 (Th2) 68,72,75,81 (Table 3). …”

Section: Resultsmentioning

confidence: 99%

“…The results of several studies have suggested potential roles of the major HSPs, such as HSP32, HSP40, HSP60, and HSP90 in affecting disease activity in RA based on in vitro evidence of HSP-induced modulation of T cell responses or cytokine profiles 55,68,72,75,81,103 . The in vitro stimulation of mononuclear cells of RA patients with human HSP60 and BHSP65 has also been shown to induce a T helper 1 to Th2 cytokine shift 72,81 .…”

Section: Discussionmentioning

confidence: 99%

“…The in vitro stimulation of mononuclear cells of RA patients with human HSP60 and BHSP65 has also been shown to induce a T helper 1 to Th2 cytokine shift 72,81 . In another study, RA patients with T cells that were reactive against human HSP60 or BHSP65 and produced Th2 cytokines had less disease activity compared with those who did not 68 .…”

Section: Discussionmentioning

confidence: 99%

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The Involvement of Heat-Shock Proteins in the Pathogenesis of Autoimmune Arthritis: A Critical Appraisal

Huang

Moudgil

2010

Seminars in Arthritis and Rheumatism

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Objectives To review the literature on the role of heat-shock proteins (HSPs) in the pathogenesis of autoimmune arthritis in animal models ans patients with rheumatoid arthritis (RA). Methods The published literature in Medline (PubMed), including our published work on the cell-mediated as well as humoral immune response to various HSPs was reviewed. Studies in both the pre-clinical animal models of arthritis as well as RA were examined critically and the data presented. Results In experimental arthritis, disease induction by different arthritogenic stimuli, including an adjuvant, led to immune response to mycobacterial HSP65 (BHSP65). However, attempts to induce arthritis by a purified HSP have not met with success. There are several reports of a significant immune response to HSP65 in RA patients. But, the issue of cause and effect is difficult to address. Nevertheless, several studies in animal models and a couple of clinical trials in RA patients have shown the beneficial effect of HSPs against autoimmune arthritis. Conclusions There is a clear association between immune response to HSPs, particularly HSP65, and the initiation and propagation of autoimmune arthritis in experimental models. The correlation is relatively less convincing in RA patients. In both cases, the ability of HSPs to modulate arthritis offers support, albeit an indirect one, for the involvement of these antigens in the disease process.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The Involvement of Heat-Shock Proteins in the Pathogenesis of Autoimmune Arthritis: A Critical Appraisal

Huang

Moudgil

2010

Seminars in Arthritis and Rheumatism

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“…The CD4 + T cells mainly synthesize and secrete cytokines, and a previous study has shown that CD4 + T cell responses to human HSP60 at the onset of juvenile idiopathic arthritis are correlated with a favourable prognosis. 10 Thus, CD4 + T cells may be involved in the immunomodulatory effects elicited by the three HSP peptides in the present study. These peptides may induce the activation of T cells by modifying cell cycle phase's distribution of CD4 + T cells from RA patients.…”

Section: Discussionmentioning

confidence: 65%

“…Heat shock proteins (HSPs) are a group of highly conserved proteins found in prokaryotic and eukaryotic cells that are induced by a number of stressors. The HSPs are classified into families according to molecular weight and they play an important role in human and experimentally induced autoimmune diseases, both as potential antigens and as intracellular chaperones involved in peptide binding to human leucocyte antigens. The role of mycobacterial HSPs in RA has been a subject of expanding interest.…”

Section: Introductionmentioning

confidence: 99%

Synthetic peptides from heat-shock protein 65 inhibit proinflammatory cytokine secretion by peripheral blood mononuclear cells from rheumatoid arthritis patients

Zhou

Wang

Feng

et al. 2013

Clin Exp Pharmacol Physiol

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1. Rheumatoid arthritis (RA) is a systemic autoimmune disease mediated by T cells. Proinflammatory cytokines plays a critical role in the pathogenesis of RA. The aim of the present study was to investigate the effects of synthetic peptides (HP-R1, HP-R2 and HP-R3), derived from the sequence of 65 kDa mycobacterial heat shock protein (HSP), on the proliferation of and cytokine secretion by peripheral blood mononuclear cells (PBMC) from RA patients. 2. The PBMC were obtained from RA patients and collected by Ficoll-Hypaque density centrifugation. Peripheral blood mononuclear cells were treated with one of the three synthetic peptides for 4 h, after which time proliferation and cytokine production were determined. The effects of the three peptides on the proliferation of PBMC were analysed by the colorimetric cell proliferation (CCK-8) assay. Cytokine production was measured in culture supernatants using specific ELISAs. 3. None of the three peptides had any significant effect on the proliferation of PBMC from healthy controls. However, the proliferation of PBMC from RA patients was inhibited by all three peptides. The production of tumour necrosis factor-α from RA patients was significantly inhibited by all three peptides. The secretion of interferon-γ was significantly suppressed by HP-R1 and HP-R2. Unlike the other two peptides, HP-R2 increased the secretion of interleukin (IL)-4. None of the peptides had any significant effect on the production of IL-10. 4. The results of the present study suggest that the synthetic peptides derived from HSP65 exhibit antiproliferative and anti-inflammatory activity, and support the potential use of synthetic peptides as therapeutic drugs in RA patients.

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Mycobacteria and Autoimmunity

Anna

2024

Infection and Autoimmunity

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In-vitro effects of Mycobacterium bovis BCG-lysate and its derived heat shock proteins on cytokines secretion by blood mononuclear cells of rheumatoid arthritis patients in comparison with healthy controls

Cited by 12 publications

References 32 publications

The Involvement of Heat-Shock Proteins in the Pathogenesis of Autoimmune Arthritis: A Critical Appraisal

The Involvement of Heat-Shock Proteins in the Pathogenesis of Autoimmune Arthritis: A Critical Appraisal

Synthetic peptides from heat-shock protein 65 inhibit proinflammatory cytokine secretion by peripheral blood mononuclear cells from rheumatoid arthritis patients

Mycobacteria and Autoimmunity

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