Immunoglobulin heavy-chain-binding protein (BiP) or glucose-regulated protein 78 (Grp78) is a vital ubiquitous resident of the endoplasmic reticulum (ER). As an intracellular chaperone, BiP correctly folds nascent polypeptides within the ER and regulates the unfolded protein response ensuring protection of the cell from denatured protein and reinforcing its anti-apoptotic role, when the cell is under stress. Additionally, BiP is a member of the heat-shock protein (HSP) 70 family and, as a stress protein, is up-regulated by conditions of reduced oxygen and glucose. Cell stress induces surface expression and secretion of BiP. Consequently, BiP is detectable in several bodily fluids including serum, synovial fluid (SF) and oviductal fluid. However, as an extracellular protein, BiP has additional properties that are quite distinct from the intracellular functions. Extracellular BiP is immunoregulatory and anti-inflammatory causing development of tolerogenic dendritic cells (DCs), induction of regulatory T-cells, abrogation of osteoclast development and function, induction of anti-inflammatory cytokine production, including interleukin (IL)-10, IL-1 receptor antagonist and soluble tumour necrosis factor (TNF)-receptor type II, and attenuation of TNFα and IL-6. Together, these functions help drive the resolution of inflammation. Disease models of inflammatory arthritis have helped to demonstrate the novel mode of action of BiP in which the pharmacokinetics and pharmacodynamics are dissociated. The three murine models to be discussed each show BiP induced long-term therapeutic protection and therefore has potential for long-lasting drug-free therapy in rheumatoid arthritis (RA).
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Conference Article|
November 17 2014
Immunoglobulin heavy-chain-binding protein (BiP): a stress protein that has the potential to be a novel therapy for rheumatoid arthritis
Gabriel S. Panayi;
Gabriel S. Panayi
1
*Academic Department of Rheumatology, King's College School of Medicine, London SE1 1UL, U.K.
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Valerie M. Corrigall
*Academic Department of Rheumatology, King's College School of Medicine, London SE1 1UL, U.K.
2To whom correspondence should be addressed (emailvalerie.corrigall@kcl.ac.uk).
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Publisher: Portland Press Ltd
Received:
August 28 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (6): 1752–1755.
Article history
Received:
August 28 2014
Citation
Gabriel S. Panayi, Valerie M. Corrigall; Immunoglobulin heavy-chain-binding protein (BiP): a stress protein that has the potential to be a novel therapy for rheumatoid arthritis. Biochem Soc Trans 1 December 2014; 42 (6): 1752–1755. doi: https://doi.org/10.1042/BST20140230
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