A 71-kD heat shock protein (hsp) from <i>Mycobacterium tuberculosis</i> has modulatory effects on experimental rat arthritis

Kingston, Ann E.; Hicks, Caroline; Colston, M. J.; Billingham, M. E. J.

doi:10.1046/j.1365-2249.1996.929628.x

Cited by 98 publications

(75 citation statements)

References 38 publications

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“…Our present findings confirm a previous report on a protective effect of mycobacterial hsp70 in experimental arthritis (23), and are well in line with the known protective effects of mycobacterial hsp65 and mycobacterial hsp10 (14,15).…”

Section: Discussionsupporting

confidence: 93%

Induction of IL-10 and Inhibition of Experimental Arthritis Are Specific Features of Microbial Heat Shock Proteins That Are Absent for Other Evolutionarily Conserved Immunodominant Proteins

Prakken

Wendling

Zee

et al. 2001

The Journal of Immunology

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Bacterial heat shock proteins (hsp) are evolutionary conserved immunodominant proteins that manifest amino acid homologies with hsp present in mammalian cells. Preimmunization with mycobacterial hsp65 has been found to protect against various forms of experimental arthritis. As these protective effects have previously been attributed to induction of self homologue cross-reactive T cell responses, the question was raised as to whether this protective effect could be extended to other highly conserved and immunodominant microbial Ags with mammalian homologues. Therefore, we immunized Lewis rats with conserved bacterial Ags (superoxide dismutase, aldolase, GAPDH, and hsp70). Although all Ags appeared highly immunogenic, we only found a protective effect in experimental arthritis after immunization with bacterial hsp70. The protective effect of hsp70 was accompanied with a switch in the subclasses of hsp70-specific Abs, suggesting the induction of Th2-like response. The most striking difference between immunization with hsp70 and all other immunodominant Ags was the expression of IL-10 found after immunization with hsp70. Even more, while immunization with hsp70 led to Ag-induced production of IL-10 and IL-4, immunization with aldolase led to increased production of IFN-γ and TNF-α. Thus, the protective effect of conserved immunodominant proteins in experimental arthritis seems to be a specific feature of hsp. Therefore, hsp may offer unique possibilities for immunological intervention in inflammatory diseases.

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Section: Discussionsupporting

confidence: 93%

Induction of IL-10 and Inhibition of Experimental Arthritis Are Specific Features of Microbial Heat Shock Proteins That Are Absent for Other Evolutionarily Conserved Immunodominant Proteins

Prakken

Wendling

Zee

et al. 2001

The Journal of Immunology

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“…Although Hsp70 shows rather pronounced proinflammatory effects which may lead to such disorders [63,76], administration of recombinant Hsp70 can attenuate experimental autoimmune diseases [42,86]. These findings indicate that extracellular Hsp70 may take part not only in the release, but also in the control of the inflammatory conditions of such disorders [63,76].…”

Section: Possible Role Of Salivary Hsp70 Under Stress Conditionsmentioning

confidence: 95%

Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Fábían

Fejérdy

Nguyen

et al. 2007

Arch. Immunol. Ther. Exp.

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Molecular chaperones were considered to be intracellular, but there is increasing evidence demonstrating their cytoprotective and immune modulator properties outside the cell. The major extracellular chaperone (Hsp70) was also found in saliva, indicating a possible effect of Hsp70 on mucosal surfaces. Here we summarize the immune-modulatory role of the 70-kDa stress protein family, with special attention on the potential impact of salivary Hsp70 on oral defense mechanisms. There are three major facets of Hsp70-induced immune activation: 1) the appearance of Hsp70 on the surface of certain tumor cells or virally infected cells, leading to their phagocytosis and subsequent lysis; 2) the role of extracellular uncomplexed Hsp70 as a danger signal, leading to the secretion of proinflammatory cytokines from antigen-presenting cells and T lymphocytes and of nitric oxide from macrophages as well as to complement activation; 3) receptor-mediated uptake of peptide-loaded Hsp70 to antigen-presenting cells and cross-presentation of the Hsp70-peptide complex as an antigen to cytotoxic T cells and natural killer lymphocytes. The immune-activating effect of salivary Hsp70 may also be highly important in oral defense, especially in areas where molecular and cellular participants of the immune response appear on the surface of the oral cavity (i.e. several lesions of the mucosa and the periodontal tissues).

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“…It has been shown to be an excellent adjuvant for antibody production [6], as well as an extremely powerful antigen, even in lipopolysaccharide (LPS) hyporesponsive mice [7]. Finally, immunization with MTBHSP70 has been shown to protect against adjuvant arthritis in rats [8]. It was demonstrated later that arthritis protection was due mainly to the induction of IL-10-producing T cells that recognize a specific MTBHSP70 peptide [9,10].…”

Section: Introductionmentioning

confidence: 99%

Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation

Detanico

Rodrigues

Sabritto

et al. 2004

Clinical and Experimental Immunology

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SUMMARYCytokines are key modulators of the immune responses that take place in the inflamed synovium of arthritis patients. Consequently, substances that can reverse the inflammatory profile of the inflamed joint are potential tools for clinical management of the disease. Mycobacterial heat shock protein 70 (MTBHSP70) has been found to protect rats from experimentally induced arthritis through the induction of interleukin (IL)-10-producing T cells. In this study, we have demonstrated that MTBHSP70 induces IL-10 production in synoviocytes from arthritis patients and peripheral blood monoculear cells (PBMCs) from both patients and healthy controls. IL-10 production was accompanied by a decrease in tumour necrosis factor (TNF)-a production by synovial cells. Separation studies showed that the target cells were mainly monocytes. Accordingly, we observed that MTBHSP70 delayed maturation of murine bone marrow-derived dendritic cells. Our results suggest that MTBHSP may act on antigen-presenting cells (APCs) to modulate the cytokine response in arthritis and support an anti-inflammatory role for this protein, suggesting that it may be of therapeutic use in the modulation of arthritis.

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A 71-kD heat shock protein (hsp) from Mycobacterium tuberculosis has modulatory effects on experimental rat arthritis

Cited by 98 publications

References 38 publications

Induction of IL-10 and Inhibition of Experimental Arthritis Are Specific Features of Microbial Heat Shock Proteins That Are Absent for Other Evolutionarily Conserved Immunodominant Proteins

Induction of IL-10 and Inhibition of Experimental Arthritis Are Specific Features of Microbial Heat Shock Proteins That Are Absent for Other Evolutionarily Conserved Immunodominant Proteins

Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Mycobacterial heat shock protein 70 induces interleukin-10 production: immunomodulation of synovial cell cytokine profile and dendritic cell maturation

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