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The complex interplay between endoplasmic reticulum stress and the NLRP3 inflammasome: a potential therapeutic target for inflammatory disorders

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posted on 2023-05-20, 23:06 authored by Chong, WC, Madhur ShastriMadhur Shastri, Gregory PetersonGregory Peterson, Rahul PatelRahul Patel, Pathinayake, PS, Dua, K, Hansbro, NG, Hsu, AC, Wark, PA, Shukla, SD, Johansen, MD, Schroder, K, Hansbro, PM
Inflammation is the result of a complex network of cellular and molecular interactions and mechanisms that facilitate immune protection against intrinsic and extrinsic stimuli, particularly pathogens, to maintain homeostasis and promote tissue healing. However, dysregulation in the immune system elicits excess/abnormal inflammation resulting in unintended tissue damage and causes major inflammatory diseases including asthma, chronic obstructive pulmonary disease, atherosclerosis, inflammatory bowel diseases, sarcoidosis and rheumatoid arthritis. It is now widely accepted that both endoplasmic reticulum (ER) stress and inflammasomes play critical roles in activating inflammatory signalling cascades. Notably, evidence is mounting for the involvement of ER stress in exacerbating inflammasome‐induced inflammatory cascades, which may provide a new axis for therapeutic targeting in a range of inflammatory disorders. Here, we comprehensively review the roles, mechanisms and interactions of both ER stress and inflammasomes, as well as their interconnected relationships in inflammatory signalling cascades. We also discuss novel therapeutic strategies that are being developed to treat ER stress‐ and inflammasome‐related inflammatory disorders.

History

Publication title

Clinical & Translational Immunology

Volume

10

Article number

e1247

Number

e1247

Pagination

1-16

ISSN

2050-0068

Department/School

School of Pharmacy and Pharmacology

Publisher

John Wiley & Sons Ltd.

Place of publication

United Kingdom

Rights statement

Copyright 2021 The Authors. This is an open access article under the terms of the Creative Commons Attribution‐ NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Repository Status

  • Open

Socio-economic Objectives

Efficacy of medications; Treatment of human diseases and conditions

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