ArticleJournal of leukocyte biology2017
Anti-inflammatory roles of p38α MAPK in macrophages are context dependent and require IL-10.
Article in Journal of leukocyte biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- The identity crisis of cryptic lncRNAs: when non-coding RNAs translate into small peptides.The EMBO journal · 2026Review
- Discrete On-DNA Screening: A Frontier for Rapid Hit-to-Lead Optimization Applied to p38α.ACS medicinal chemistry letters · 2026Article
- Network Rewiring in the Aging Immune System: From Chronic Inflammation to Age-Related Pathologies.Cells · 2026Review
- Hyperglycemia Modulates the Expression of MAPK13, TSP1, and CXCR2 During Wound Healing in Sprague Dawley Rats.Biology · 2025Article
- Natural genetic variation in wild-derived mice controls host survival and transcriptional responses during endotoxic shock.ImmunoHorizons · 2025Article
- Pulmonary hypertension: etiology and anti-inflammatory treatment pathways of natural products.Frontiers in pharmacology · 2025Review
- A small molecule p38α MAPK inhibitor, MW150, attenuates behavioral deficits and neuronal dysfunction in a mouse model of mixed amyloid and vascular pathologies.Brain, behavior, & immunity - health · 2024Article
- Multi-System-Level Analysis with RNA-Seq on Pterygium Inflammation Discovers Association between Inflammatory Responses, Oxidative Stress, and Oxidative Phosphorylation.International journal of molecular sciences · 2024Article
- Host Genetic Variation Has a Profound Impact on Immune Responses Mediating Control of Viral Load in Chronic Gammaherpesvirus Infection.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- A pre-market interventional, single-arm clinical investigation of a new topical lotion based on hyaluronic acid and peptides, EGYFILBMC musculoskeletal disorders · 2023Article
- Long Noncoding RNA U90926 Is Induced in Activated Macrophages, Is Protective in Endotoxic Shock, and Encodes a Novel Secreted Protein.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- The Effect and Mechanism of Corilagin fromFoods (Basel, Switzerland) · 2023Article
- Emerging role of protein modification in inflammatory bowel disease.Journal of Zhejiang University. Science. B · 2022Review
- Polypharmacologic Reprogramming of Tumor-Associated Macrophages toward an Inflammatory Phenotype.Cancer research · 2022Article
- Divergent Genetic Regulation of Nitric Oxide Production between C57BL/6J and Wild-Derived PWD/PhJ Mice Controls Postactivation Mitochondrial Metabolism, Cell Survival, and Bacterial Resistance in Dendritic Cells.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization.International journal of molecular sciences · 2021Article
- Integration of Metabolomics and Transcriptomicsto Comprehensively Evaluate the Metabolic Effects ofAnimals : an open access journal from MDPI · 2021Article
- Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS-induced acute lung injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- p38 MAP Kinase Signaling in Microglia Plays a Sex-Specific Protective Role in CNS Autoimmunity and Regulates Microglial Transcriptional States.Frontiers in immunology · 2021Article
- Identification of novel loci controlling inflammatory bowel disease susceptibility utilizing the genetic diversity of wild-derived mice.Genes and immunity · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The p38 MAPK pathway was originally identified as a master regulator of proinflammatory cytokine production by myeloid cells. Numerous drugs targeting this kinase showed promise in preclinical models of inflammatory disease, but so far, none have shown efficacy in clinical trials. The reasons behind this are unclear, but may, in part, be explained by emerging anti-inflammatory functions of this kinase or overly refined selectivity of second-generation pharmacologic inhibitors. Here, we show that p38α signaling in macrophages plays pro- and anti-inflammatory functions in vivo and in vitro, with the outcome depending on the stimulus, output, kinetics, or mode of kinase inhibition (genetic vs. pharmacologic). Different pharmacologic inhibitors of p38 exhibit opposing effects, with second-generation inhibitors acting more specifically but inhibiting anti-inflammatory functions. Functionally, we show that the anti-inflammatory functions of p38α in macrophages are critically dependent on production of IL-10. Accordingly, in the absence of IL-10, inhibition of p38α signaling in macrophages is protective in a spontaneous model of colitis. Taken together, our results shed light on the limited clinical efficacy of drugs targeting p38 and suggest that their therapeutic efficacy can be significantly enhanced by simultaneous modulation of p38-dependent anti-inflammatory mediators, such as IL-10.
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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.