Heat Shock Proteins gp96 and hsp70 Activate the Release of Nitric Oxide by APCs

Panjwani, Naveed; Popova, Lana; Srivastava, Pramod K.

doi:10.4049/jimmunol.168.6.2997

Cited by 240 publications

(148 citation statements)

References 49 publications

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“…For example, HSP derived from murine liver and kidney has been shown to be able to activate dendritic cells and macrophages. 23 Moreover, cells that were triggered to upregulate cell-surface HSP70 could induce TLR2 and TLR4 signalling in macrophages. 24 25 In addition to these reports of highly purified HSP, other papers have described distinct activation of TLR signalling after HSP binding.…”

Section: Innate Immunitymentioning

confidence: 99%

Heat-shock proteins induce T-cell regulation of chronic inflammation

2005

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Section: Innate Immunitymentioning

confidence: 99%

Heat-shock proteins induce T-cell regulation of chronic inflammation

2005

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“…macrophages) [19,53,77] and on T lymphocytes [12] induces the secretion of proinflammatory cytokines. Extracellular Hsp70 also induces inducible nitric oxide (NO) synthase and NO release from macrophages [61]. Uncomplexed Hsp70 may also activate NK lymphocytes (NK cells) [51,53].…”

Section: Immuno−modulatory Effects Of Hsp70mentioning

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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“…HSP70 has been reported to activate the innate immune response, resulting in the maturation of DCs, [13][14][15] the upregulation of proinflammatory cytokines [13][14][15][16] and nitric oxide release by APCs. 17 Rapid intracellular Ca 2 þ flux 18 and CD14-dependent toll-like receptor (TLR) 2-and TLR4-mediated activation of the MyD88/interleukin-1 receptor associated kinase (IRAK)/nuclear factor (NF)-kappaB signal transduction pathway 18,19 have been reported as consequences of HSP70 binding to cell surface receptors on APCs. However, this has been the matter of some debate since recent reports 20,21 could not confirm these observations.…”

Section: Introductionmentioning

confidence: 99%

Secretory heat-shock protein as a dendritic cell-targeting molecule: a new strategy to enhance the potency of genetic vaccines

Shen

et al. 2004

Gene Ther

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DNA vaccines are an appealing strategy for inducing cytotoxic T-lymphocyte and antibody responses against tumor cells as well as infectious agents. Dendritic cells (DCs) play a critical role in inducing immune responses, but their potential is not fully utilized in the DNA vaccine setting since they take up only a minor fraction of the injected DNA. Here we describe a novel DNA vaccination strategy based on the targeting of a modified tumor-associated antigen, the human papilloma virus (HPV) type 16 E7 protein, to DCs by a heat-shock protein (HSP) to enhance antigen presentation and immune responses. Specifically, a chimerical HPV-E7 and HSP70 fusion gene preceded with a leader sequence was constructed. When mice were immunized with this construct, the DNA is taken up by various types of cells, which then produce and secrete an HPV-E7-HSP70 fusion protein that is targeted to DCs by the HSP70 portion of the chimerical molecule for antigen presentation. In studies to test the efficacy of this strategy, we demonstrated that DNA vaccination with this secretory HPV-E7-HSP70 construct strongly enhanced an antigen-specific CD8 þ T-cell response as well as a specific B-cell response in mice. Furthermore, this immunization approach not only protected mice against lethal challenge with an HPV E7-expressing tumor line (TC-1), but also showed a therapeutic effect against established tumors. The results of this study indicate that secretory HSPs can be broadly used to target tumorassociated antigens to DCs to enhance antigen-specific immune responses. Gene Therapy (2004) 11, 924-932.

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Heat Shock Proteins gp96 and hsp70 Activate the Release of Nitric Oxide by APCs

Cited by 240 publications

References 49 publications

Heat-shock proteins induce T-cell regulation of chronic inflammation

Heat-shock proteins induce T-cell regulation of chronic inflammation

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

Secretory heat-shock protein as a dendritic cell-targeting molecule: a new strategy to enhance the potency of genetic vaccines

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