The interplay between endoplasmic reticulum stress and inflammation

Hasnain, Sumaira Z.; Lourie, Rohan; Das, Indrajit; Chen, Alice C-H; McGuckin, Michael A.

doi:10.1038/icb.2011.112

Cited by 235 publications

(231 citation statements)

References 114 publications

(137 reference statements)

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“…ER stress has been shown to intertwine with inflammation and involve diverse biological events in leukocytes, such as monocytes, macrophages, and lymphocytes (13,25). Physiologically, XBP1 is necessary for differentiation of B cells, NK cells, and macrophages, although there is no detected basal IRE-1 activity for naive T cells and monocytes from spleen (17).…”

Section: Discussionmentioning

confidence: 99%

“…To characterize the ER stress in the infiltrated neutrophils, we first collected the neutrophils from BALF of ALI mice. The key factor in the initiation of the UPR is a heat shock protein, GRP78, which is the most abundant ER chaperon (25). In mammals, there are three major ER membraneassociated proteins acting as ER stress sensors, IRE1a, PERK, and ATF6.…”

Section: Er Stress Was Enhanced In Neutrophils In An Ali Mice Modelmentioning

confidence: 99%

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Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Chen

Jia

et al. 2015

The Journal of Immunology

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Diverse clinical factors, including intestinal ischemia, contribute to acute lung injury (ALI), which has up to a 40% mortality rate. During the development of lung injury an immune response is elicited that exacerbates the lung insult. Neutrophils have been well studied in mediating the pulmonary insults through an assortment of mechanisms, such as release of granule contents and production of proinflammatory cytokines due to the overactivation of complement and cytokines. In this study, we found that enhanced endoplasmic reticulum (ER) stress was observed in infiltrated neutrophils in the early stage of an ALI mice model. In neutrophils, complement 5a (C5a) inspires strong ER stress through inositol-requiring kinase 1a and, to a less extent, the protein kinase R–like ER kinase signaling pathway. The granule release induced by C5a was ER stress mediated. Knowkdown of X-box–binding protein 1, a downstream signaling molecule of inositol-requiring kinase 1a, impaired granule release, based on myeloperoxidase production. Further analysis revealed that C5a induced ER stress by binding to C5a receptor in neutrophils. Using xbpf/f MRP8-cre mice in which X-box–binding protein 1 is deficient specifically in neutrophils and ER stress is deprived, we confirmed that ER stress in neutrophils was required for granule release in vivo and led to ALI, whereas dampening ER stress in neutrophils substantially alleviated ALI. Taken together, our results demonstrated that C5a receptor–mediated ER stress induced granule release in neutrophils, contributing to the development of ALI. This novel mechanism suggests a new potential therapeutic target in autophagy regulation for ALI.

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Section: Discussionmentioning

confidence: 99%

Section: Er Stress Was Enhanced In Neutrophils In An Ali Mice Modelmentioning

confidence: 99%

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Chen

Jia

et al. 2015

The Journal of Immunology

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“…Several autoimmune/inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, neurodegenerative and neuromuscular inflammatory diseases and diabetes lead to activation of the UPR in affected tissues [10,11]. There is evidence of ongoing UPR in the pancreatic islets of type 1 diabetic patients [12], in intestinal cells from patients affected by ulcerative colitis or Crohn's disease and in synovial tissues from patients with rheumatoid arthritis [5].…”

Section: The Cross-talk Between the Upr And Inflammationmentioning

confidence: 99%

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

2012

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Protein synthesis is increased by several-fold in stimulated pancreatic beta cells. Synthesis and folding of (pro)insulin takes place in the endoplasmic reticulum (ER), and beta cells trigger the unfolded protein response (UPR) to upgrade the functional capacity of the ER. Prolonged or excessive UPR activation contributes to beta cell dysfunction and death in type 2 diabetes, but there is another side of the UPR that may be of particular relevance for autoimmune type 1 diabetes, namely, the crosstalk between the UPR and innate immunity/inflammation. Recent evidence, discussed in this review, indicates that both saturated fats and inflammatory mediators such as cytokines trigger the UPR in pancreatic beta cells. The UPR potentiates activation of nuclear factor κB, a key regulator of inflammation. Two branches of the UPR, namely IRE1/XBP1s and PERK/ATF4/CHOP, mediate the UPR-induced sensitisation of pancreatic beta cells to the proinflammatory effects of cytokines. This can contribute to the upregulation of local inflammatory mechanisms and the aggravation of insulitis. The dialogue between the UPR and inflammation may provide an explanation for the parallel increase in the prevalence of childhood obesity and type 1 diabetes.

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“…Glucocorticoids suppress inflammatory responses (Barnes, 1998) and inflammatory factors could enhance ER stress (Hasnain et al, 2012). Because the influence of DEX on Muc2 biosynthesis could be via direct effects on ER stress in goblet cells and/or mediated indirectly via suppression of inflammation, we assessed molecular and histological markers of inflammation.…”

Section: Glucocorticoids Suppress Intestinal Inflammation In Winnie Micementioning

confidence: 99%

Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

Das¹,

Png²,

Oancea³

et al. 2013

J Cell Biol

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The interplay between endoplasmic reticulum stress and inflammation

Cited by 235 publications

References 114 publications

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Endoplasmic Reticulum Stress of Neutrophils Is Required for Ischemia/Reperfusion–Induced Acute Lung Injury

Signalling danger: endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

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