HSP90, HSP70, and GAPDH Directly Interact with the Cytoplasmic Domain of Macrophage Scavenger Receptors

Nakamura, Toshinobu; Hinagata, Jun-ichi; Tanaka, Toshiki; Imanishi, Takeshi; Wada, Youichiro; Kodama, Tatsuhiko; Doi, Takefumi

doi:10.1006/bbrc.2001.6271

Cited by 41 publications

(28 citation statements)

References 45 publications

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“…These results were independently corroborated by others [44]. Presently, the list of putative Hsp72 receptors now includes the scavenger receptor, CD36 [45,46], the costimulatory molecule, CD40 [47], the low-density lipoprotein receptor-related protein CD91 [48][49][50][51], Lox-1 [45,52] and SR-A, another member of the scavenger superfamily [53,54].…”

Section: Hsp70 Receptorsupporting

confidence: 57%

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72

Asea

2006

CIR

142

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Heat shock proteins exert their beneficial effects via basically two modes of action depending on their relative location within the host. Intracellular heat shock proteins found within cells serve a cytoprotective role by chaperoning naïve, misfolded and/or denatured proteins in response to stressful stimuli by a process known as the stress response. However, stressful stimuli also induce the release of intracellular heat shock proteins into the extracellular milieu and circulation. The extracellular heat shock protein proteins serve a cytostimulatory role by initiating immune responses designed to fend off microbial infection and destroy neoplastic transformed cells. This review will briefly cover recent advances into elucidating the mechanism(s) by which stress induces the release of heat shock proteins into the circulation, how it initiates immune responses and suggest the possible biological significance of circulating Hsp to the host.

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Section: Hsp70 Receptorsupporting

confidence: 57%

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72

Asea

2006

CIR

142

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“…For example, GAPDH associates with the cell surface in both murine and human macrophages and is a functional transferrin receptor involved in endosomal trafficking (47). GAPDH was also shown to directly interact with the cytoplasmic domain of the macrophage scavenger receptor and therefore was hypothesized to be involved in macrophage scavenger receptor-related functions (49). Although GAPDH is an essential glycolytic enzyme, it seems that the interaction with LL-37 and indeed its many other interacting partners do not lead to complete inhibition of enzyme function (as clearly revealed by enzyme inhibition studies).…”

Section: Discussionmentioning

confidence: 99%

Intracellular Receptor for Human Host Defense Peptide LL-37 in Monocytes

Mookherjee

Lippert

Hamill

et al. 2009

The Journal of Immunology

142

122

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The human cationic host defense peptide LL-37 has a broad range of immunomodulatory, anti-infective functions. A synthetic innate defense regulator peptide, innate defense regulator 1 (IDR-1), based conceptually on LL-37, was recently shown to selectively modulate innate immunity to protect against a wide range of bacterial infections. Using advanced proteomic techniques, ELISA, and Western blotting procedures, GAPDH was identified as a direct binding partner for LL-37 in monocytes. Enzyme kinetics and mobility shift studies also indicated LL-37 and IDR-1 binding to GAPDH. The functional relevance of GAPDH in peptide-induced responses was demonstrated by using gene silencing of GAPDH with small interfering RNA (siRNA). Previous studies have established that the induction of chemokines and the anti-inflammatory cytokine IL-10 are critical immunomodulatory functions in the anti-infective properties of LL-37 and IDR-1, and these functions are modulated by the MAPK p38 pathway. Consistent with that, this study demonstrated the importance of the GAPDH interactions with these peptides since gene silencing of GAPDH resulted in impaired p38 MAPK signaling, downstream chemokine and cytokine transcriptional responses induced by LL-37 and IDR-1, and LL-37-induced cytokine production. Bioinformatic analysis, using InnateDB, of the major interacting partners of GAPDH indicated the likelihood that this protein can impact on innate immune pathways including p38 MAPK. Thus, this study has demonstrated a novel function for GAPDH as a mononuclear cell receptor for human cathelicidin LL-37 and immunomodulatory IDR-1 and conclusively demonstrated its relevance in the functioning of cationic host defense peptides.

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“…There are a few reports addressing the potential signaling pathways/processes involved following SR-A and MARCO binding. One study, using a synthetic bovine SR-A construct, demonstrated that heat-shock proteins HSP90 and HSP70, in addition to glyceraldehyde 3-phosphate dehydrogenase bound to the cytoplasmic N-terminus of the SR [56]. The involvement of HSP could help explain the SR ligand internalization process.…”

Section: Macrophage Surface Receptors Involved In Silica Toxicitymentioning

confidence: 99%

Silica binding and toxicity in alveolar macrophages

Hamilton

Thakur

Holian

2008

Free Radical Biology and Medicine

333

242

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Inhalation of the crystalline form of silica is associated with a variety of pathologies from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science researchers looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage (AM) interacts with the inhaled silica particle and the consequences of silicainduced toxicity on the cellular level. Based on experimental results, several rationales have been developed on exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica) triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species (RNS) are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, where silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis is described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.

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HSP90, HSP70, and GAPDH Directly Interact with the Cytoplasmic Domain of Macrophage Scavenger Receptors

Cited by 41 publications

References 45 publications

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72

Intracellular Receptor for Human Host Defense Peptide LL-37 in Monocytes

Silica binding and toxicity in alveolar macrophages

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