ArticleScience signaling2015
Extracellular signal-regulated kinase 5 promotes acute cellular and systemic inflammation.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Transcriptional insights into the CD8Journal of translational medicine · 2020Pooled it
- Inhibition of ERK5 activity ameliorates osteoarthritis by suppressing NLRP3 inflammasome-mediated chondrocyte pyroptosis.Bone research · 2026Article
- XMD8-92 and JWG-045 exhibit anti-ferroptotic activities, independently of inhibiting ERK5.Scientific reports · 2026Article
- Bone and Extracellular Signal-Related Kinase 5 (ERK5).Biomolecules · 2024Review
- The Perspectives of Platelet Proteomics in Health and Disease.Biomedicines · 2024Review
- The role of microglia in Neuroinflammation associated with cardiopulmonary bypass.Frontiers in cellular neuroscience · 2024Review
- Effects of Radiation-Induced Skin Injury on Hyaluronan Degradation and Its Underlying Mechanisms.Molecules (Basel, Switzerland) · 2023Article
- Developing A Baseline Metabolomic Signature Associated with COVID-19 Severity: Insights from Prospective Trials Encompassing 13 U.S. Centers.Metabolites · 2023Article
- An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.Circulation research · 2023Article
- Comparison of the efficacy of the mouse hepatic and renal antioxidant systems against inflammation-induced oxidative stress.Cell biochemistry and biophysics · 2023Article
- The significance of ERK5 catalytic-independent functions in disease pathways.Frontiers in cell and developmental biology · 2023Review
- Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation.Cell chemical biology · 2022Article
- Retinal Inflammation, Oxidative Stress, and Vascular Impairment Is Ablated in Diabetic Mice Receiving XMD8-92 Treatment.Frontiers in pharmacology · 2021Article
- Kinase inhibition in autoimmunity and inflammation.Nature reviews. Drug discovery · 2021Review
- Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for….Biochemical Society transactions · 2020Review
- Single Cell Transcriptomics Implicate Novel Monocyte and T Cell Immune Dysregulation in Sarcoidosis.Frontiers in immunology · 2020Article
- Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury.Cell & bioscience · 2020Article
- Taoren Honghua Drug Attenuates Atherosclerosis and Plays an Anti-Inflammatory Role in ApoE Knock-Out Mice and RAW264.7 Cells.Frontiers in pharmacology · 2020Article
- Cortistatin exerts antiproliferation and antimigration effects in vascular smooth muscle cells stimulated by Ang II through suppressing ERK1/2, p38 MAPK, JNK and ERK5 signaling pathways.Annals of translational medicine · 2019Article
- MEK5/ERK5 activation regulates colon cancer stem-like cell properties.Cell death discovery · 2019Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory critical illness is a syndrome that is characterized by acute inflammation and organ injury, and it is triggered by infections and noninfectious tissue injury, both of which activate innate immune receptors and pathways. Although reports suggest an anti-inflammatory role for the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 5 (ERK5), we previously found that ERK5 mediates proinflammatory responses in primary human cells in response to stimulation of Toll-like receptor 2 (TLR2). We inhibited the kinase activities and reduced the abundances of ERK5 and MEK5, a MAPK kinase directly upstream of ERK5, in primary human vascular endothelial cells and monocytes, and found that ERK5 promoted inflammation induced by a broad range of microbial TLR agonists and by the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Furthermore, we found that inhibitors of MEK5 or ERK5 reduced the plasma concentrations of proinflammatory cytokines in mice challenged with TLR ligands or heat-killed Staphylococcus aureus, as well as in mice that underwent sterile lung ischemia-reperfusion injury. Finally, we found that inhibition of ERK5 protected endotoxemic mice from death. Together, our studies support a proinflammatory role for ERK5 in primary human endothelial cells and monocytes, and suggest that ERK5 is a potential therapeutic target in diverse disorders that cause inflammatory critical illness.
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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.