Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disease characterized by the attack of the immune system on the body’s healthy joint lining and degeneration of articular structures. This disease involves an increased release of inflammatory mediators in the affected joint that sensitize sensory neurons and create a positive feedback loop to further enhance their release. Among these mediators, the cytokines and neuropeptides are responsible for the crippling pain and the persistent neurogenic inflammation associated with RA. More importantly, specific proteins released either centrally or peripherally have been shown to play opposing roles in the pathogenesis of this disease: an inflammatory role that mediates and increases the severity of inflammatory response and/or an anti-inflammatory and protective role that modulates the process of inflammation. In this review, we will shed light on the neuroimmune function of different members of the heat shock protein (HSPs) family and the complex manifold actions that they exert during the course of RA. Specifically, we will focus our discussion on the duality in the mechanism of action of Hsp27, Hsp60, Hsp70, and Hsp90.
Highlights
IntroductionPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
Effort has been made to target heat shock proteins (Hsp27, Heat shock protein 60 (Hsp60), Hsp70, and Hsp90), a family of molecular chaperones that participate in immune response as part of their noncanonical function, as they have been found to become highly expressed during inflammation
The results showed that Heat shock protein 27 (Hsp27) increased the production of IL-8, a pro-inflammatory cytokine, and dampened the anti-inflammatory response by decreasing the production of transforming growth factor β1 (TGF-β1) in smooth muscle cells and astrocytes [26], showing Hsp270 s ability to enhance neurogenic inflammation
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. RA progression is classically divided into four stages [2]: (i) the immune system misguidedly attacks joint tissue, causing swelling and inflammation of the synovium (stage 1); (ii) the swelling worsens and the connective tissue surrounding the joint becomes damaged (stage 2); (iii) the characteristic symptoms of inflammation are more severe; and screening tests become less significant for diagnosis as the physical deformity in patients’ extremities is distinctive (stage 3); (iv) the joints and cartilage are completely destroyed and the bones become fused together (stage 4) While progression through these stages takes a considerable number of years, the patients persistently suffer from tenderness, joint stiffness, swollen joints, fever, fatigue, and loss of appetite. About 40% of the people who have rheumatoid arthritis experience signs and symptoms that don’t involve the joints such as in the skin, eyes, and kidneys, especially at later stages [3]
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