ArticleMolecular and cellular biology2014
PERK-dependent activation of JAK1 and STAT3 contributes to endoplasmic reticulum stress-induced inflammation.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed, 229 citations in OpenAlex.
- PERK deficiency amplifies molecular, structural, and network vulnerability to repetitive mild traumatic brain injury.Neurobiology of disease · 2026Article
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Discovery of a pyrazolopyridine alkaloid that mitigates neuronal ER stress and age-related decline.Communications biology · 2026Article
- JAK1/2 inhibitor ruxolitinib reduces aggregates in cardiac proteinopathy.EMBO molecular medicine · 2026Article
- PERK Deficiency Amplifies Molecular, Structural, and Network Vulnerability to Repetitive Mild Traumatic Brain Injury.bioRxiv : the preprint server for biology · 2026Article
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- IFNγ-induced antigen loss in chimeric antigen receptor-T cell therapy.Frontiers in immunology · 2026Article
- Traditional Chinese botanical medicines and plant-derived bioactive compounds in amyotrophic lateral sclerosis: mechanistic evidence, translational challenges, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Dimethyl fumarate ameliorated pyroptosis in contrast-induced acute renal injury by regulating endoplasmic reticulum stress and JAK2-STAT3 pathway.Renal failure · 2025Article
- New Role of Protein Misfolding Corrector in the ER Stress-Inflammation Axis: Possible Therapeutic Indication in Neuronal and Epithelial Tumor Cells.International journal of molecular sciences · 2025Article
- Article
- Chronic hypoxia induces liver injury via PKCδ/ASMase-driven ceramide accumulation and endoplasmic reticulum stress in rats.Lipids in health and disease · 2025Article
- Traditional and New Views on MSI-H/dMMR Endometrial Cancer.Biomolecules · 2025Review
- Integrated stress response in Behçet disease: expression analyses in peripheral blood and synovial monocytes.Rheumatology international · 2025Article
- Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Review
- Exploring the Therapeutic Potential of Glycyrrhiza Compounds in Alzheimer's Disease: A Comprehensive Review.Current topics in medicinal chemistry · 2025Review
- Integration of Network Pharmacology, Molecular Docking, and Experimental Validation to Identify the Effect of EGCG on Alleviating Chondrocyte Inflammatory Damage by Targeting ER Stress-STAT3 Crosstalk.Journal of inflammation research · 2025Article
- Evidence for the Involvement of Gene Regulation of Inflammatory Molecules in the Accumulation of Intracellular Cholesterol: The Mechanism of Foam Cell Formation in Atherosclerosis.Current medicinal chemistry · 2025Article
- Beta-adrenergic stimulation promotes an endoplasmic reticulum stress-dependent inflammatory program in salivary gland epithelial cells.Clinical and experimental immunology · 2024Article
- 1-L Transcription in Prion Diseases.International journal of molecular sciences · 2024Article
86 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Neuroinflammation and endoplasmic reticulum (ER) stress are associated with many neurological diseases. Here, we have examined the interaction between ER stress and JAK/STAT-dependent inflammation in glial cells. We show that ER stress is present in the central nervous system (CNS) concomitant with inflammation and astrogliosis in the multiple sclerosis (MS) mouse model of experimental autoimmune encephalomyelitis (EAE). Astrocytes do not easily succumb to ER stress but rather activate an inflammatory program involving activation of STAT3 in a JAK1-dependent fashion. ER stress-induced activation of the JAK1/STAT3 axis leads to expression of interleukin 6 (IL-6) and several chemokines. Moreover, the activation of STAT3 signaling is dependent on PERK, a central component of the ER stress response, which we show is phosphorylated by JAK1. Disruption of PERK abrogates ER stress-induced activation of STAT3 and subsequent gene expression. Additionally, ER-stressed astrocytes, via paracrine signaling, can stimulate activation of microglia, leading to production of IL-6 and oncostatin M (OSM). These IL-6 cytokines can then synergize with ER stress in astrocytes to drive inflammation. Together, this work describes a new PERK/JAK1/STAT3 signaling pathway that elicits a feed-forward inflammatory loop involving astrocytes and microglia to drive neuroinflammation, which may be relevant in diseases such as MS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.