Humoral Immunity to Stress Proteins and Periodontal Disease

Lopatin, Dennis E.; Shelburne, Charles E.; Poperin, Neal Van; Kowalski, Charles J.; Bagramian, Robert A.

doi:10.1902/jop.1999.70.10.1185

Cited by 43 publications

(62 citation statements)

References 42 publications

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“…In advanced phases of these processes, a higher amount of Hsp70 will be present also from the inflammatory exudate of the blood sera and from the lysed cells and lysed bacteria [47,62,78]. In these cases, the importance of salivary Hsp70 can be considered as a large reservoir of a continuous supply of damaged Hsp70 molecules.…”

Section: The Possible Defense Functions Of Salivary Hsp70 In Mucosal mentioning

confidence: 99%

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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Section: The Possible Defense Functions Of Salivary Hsp70 In Mucosal mentioning

confidence: 99%

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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“…Therefore, its abilities to induce cytokines in monocytes (32) or to function as nominal Ag for B and T cell responses (Ref. 33 and our own unpublished observations) were distinct from its chaperoning function in preferential loading of the AChR epitope in 0401 ϩ APC.…”

Section: Discussionmentioning

confidence: 99%

Major Differences in Antigen-Processing Correlate with a Single Arg71↔Lys Substitution in HLA-DR Molecules Predisposing to Rheumatoid Arthritis and with Their Selective Interactions with 70-kDa Heat Shock Protein Chaperones

Roth

Willcox

Rzepka

et al. 2002

The Journal of Immunology

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Several HLA-DR alleles are genetically associated with rheumatoid arthritis. DRB1*0401 predominates in Northern Europe and has a characteristic 70QKRAA motif. This sequence contacts bound peptides and the TCR. Further interactions have been suggested with additional proteins during Ag loading. We explored the much stronger processing/presentation of full-length recombinant human acetylcholine receptor α subunit to a specific T cell clone by APC from DRB1*0401+ than *0408+ donors. Using DR*04 transfectants, we show that this difference results largely from the single Lys71↔Arg interchange (0401↔0408), which scarcely affects epitope binding, rather than from any other associated polymorphism. Furthermore, we proved our recombinant polypeptides to contain the Escherichia coli 70-kDa heat shock protein molecule DnaK and its requirement for efficient processing and presentation of the epitope by DRB1*0401+ cells. According to a recent report, 70-kDa heat shock protein chaperones preferentially bind to the QKRAA, rather than the QRRAA, motif. Variations between the shared epitope motifs QKRAA and QRRAA are emphasized by underlining. We propose that such interactions enhance the intracellular epitope loading of *0401 molecules. They may thus broaden immune responses to pathogens and at least partially explain the distinct contributions of DRB1*0401 and other alleles to disease predisposition.

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“…Furthermore, the higher serum level of specific human antibodies against microbial HSPAs, but importantly not against HSPAs of human origin, tends to positively correlate with healthier periodontal tissues (21), indicating that microbial heat shock proteins are immunodominant antigens triggering adaptive immunity of the organism to contribute to protection against oral microorganisms, and to maintain gingival health (21). Furthermore, the peptide binding C-terminal portion of microbial HSPAs strongly enhances serum IgG response triggered by certain (microbial) antigenic peptides following binding of C-terminal portion to the antigen at issue (10), which may also contribute to improved gingival health.…”

Section: Immune Surveillance and Periodontal Healthmentioning

confidence: 98%

The Role of Molecular Chaperones (Hspas/Hsp70S) in Oral Health and Oral Inflammatory Diseases: A Review

et al. 2009

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Heat shock proteins of the 70kDa family (HSPAs/HSP70s) are major molecular chaperones and cytokines of most cells and microbes, extracellular and interstitial fluids, blood, synovial fluids and secretory body fluids like saliva. The induction of human HSPAs plays an important role at cellular level under most stress conditions; whereas microbial HSPAs improve microbial tolerance to environmental changes, and improve virulence and resistance against antimicrobial peptides. Extracellular HSPAs reveal cytoprotective properties and are involved in numerous physiological and pathological events, including modulation of cytokine release and immunity. Accordingly, HSPAs play a role in the maintenance of pulpal health, and the repair of injured dental hard tissues. HSPAs also play a role in stress adaptation of periodontal tissues, and in the maintenance of periodontal and mucosal health including defense against microbes, prevention of mucosal allergic reactions, and facilitation of healing of ulcers and wounds. Despite their advantageous effects maintaining health of several oral tissues, HSPAs are likely to play a role in the disadvantageous amplification of pulpal inflammatory response to bacteria, and in the formation of several periapical inflammatory lesions. HSPAs may also induce gingivitis under certain conditions, and play a role in the progression of periodontal bone defects. HSPAs may also play a role in atopic-type allergic reactions, autoimmune disorders, and haptenation in certain cases. Based on the above data, it can be assumed that HSPAs play an important role in oral defense under healthy conditions; however, their role is somewhat “Janus-faced” under pathological conditions.

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Humoral Immunity to Stress Proteins and Periodontal Disease

Cited by 43 publications

References 42 publications

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

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

Major Differences in Antigen-Processing Correlate with a Single Arg71↔Lys Substitution in HLA-DR Molecules Predisposing to Rheumatoid Arthritis and with Their Selective Interactions with 70-kDa Heat Shock Protein Chaperones

The Role of Molecular Chaperones (Hspas/Hsp70S) in Oral Health and Oral Inflammatory Diseases: A Review

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