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Major histocompatibility complex I‐induced endoplasmic reticulum stress mediates the secretion of pro‐inflammatory muscle‐derived cytokines

Thoma, A, Earl, KE, Goljanek‐Whysall, K and Lightfoot, AP (2022) Major histocompatibility complex I‐induced endoplasmic reticulum stress mediates the secretion of pro‐inflammatory muscle‐derived cytokines. Journal of Cellular and Molecular Medicine. ISSN 1582-1838

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Abstract

Major histocompatibility complex (MHC) I is an important component of intracellular antigen presentation. However, improper expression of MHC I upon the cell surface has been associated with several autoimmune diseases. Myositis is a rare acquired autoimmune disease which targets skeletal muscle, and MHC I overexpression on the surface of muscle fibres and immune cell infiltration are clinical hallmarks. MHC I overexpression may have an important pathogenic role, mediated by the activation of the endoplasmic reticulum (ER) stress response. Given the evidence that muscle is a diverse source of cytokines, we aimed to investigate whether MHC I overexpression can modify the profile of muscle-derived cytokines and what role the ER stress pathway may play. Using C2C12 myoblasts we overexpressed MHC I with a H-2kb vector in the presence or absence of salubrinal an ER stress pathway modifying compound. MHC I overexpression induced ER stress pathway activation and elevated cytokine gene expression. MHC I overexpression caused significant release of cytokines and chemokines, which was attenuated in the presence of salubrinal. Conditioned media from MHC I overexpressing cells induced in vitro T-cell chemotaxis, atrophy of healthy myotubes and modified mitochondrial function, features which were attenuated in the presence of salubrinal. Collectively, these data suggest that MHC I overexpression can induce pro-inflammatory cytokine/chemokine release from C2C12 myoblasts, a process which appears to be mediated in-part by the ER stress pathway.

Item Type: Article
Uncontrolled Keywords: 0304 Medicinal and Biomolecular Chemistry; 0601 Biochemistry and Cell Biology; 1103 Clinical Sciences; Biochemistry & Molecular Biology
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH301 Biology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
SWORD Depositor: A Symplectic
Date Deposited: 29 Nov 2022 14:27
Last Modified: 29 Nov 2022 14:27
DOI or Identification number: 10.1111/jcmm.17621
URI: https://researchonline.ljmu.ac.uk/id/eprint/18234

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