ArticleInfection and immunity2013
MAPK-activated protein kinase 2 contributes to Clostridium difficile-associated inflammation.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pooled it
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- The Use of Bacteria and Their Toxins as Antitumor Agents: Present and Future.Microorganisms · 2026Review
- ApoE COG 133 mimetic peptide improves survival, infection burden, andExperimental biology and medicine (Maywood, N.J.) · 2025Article
- Exploring the Toxin-Mediated Mechanisms inMicroorganisms · 2024Review
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- Characterization and Stability of a Novel Toxin in Scallop Mantle Tissue.Foods (Basel, Switzerland) · 2023Article
- Identification and Functional Analysis ofGenes · 2022Article
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- The Inflammasome and Type-2 Immunity inClinics in colon and rectal surgery · 2020Review
- TheScience signaling · 2020Article
- ProbingFrontiers in microbiology · 2019Article
- TPL2 Is a Key Regulator of Intestinal Inflammation in Clostridium difficile Infection.Infection and immunity · 2018Article
- A potential strategy for reducing cysts in autosomal dominant polycystic kidney disease with a CFTR corrector.The Journal of biological chemistry · 2018Article
- Cysteine Protease-Mediated Autocleavage ofCellular and molecular gastroenterology and hepatology · 2018Article
- Expression and (Lacking) Internalization of the Cell Surface Receptors ofFrontiers in microbiology · 2018Article
- Quantitative Phosphoproteome Analysis ofFrontiers in microbiology · 2018Article
- The role of toxins in Clostridium difficile infection.FEMS microbiology reviews · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Clostridium difficile infection (CDI) results in toxin-induced epithelial injury and marked intestinal inflammation. Fecal markers of intestinal inflammation correlate with CDI disease severity, but regulation of the inflammatory response is poorly understood. Previous studies demonstrated that C. difficile toxin TcdA activates p38 kinase in tissue culture cells and mouse ilium, resulting in interleukin-8 (IL-8) release. Here, we investigated the role of phosphorylated mitogen-activated protein kinase (MAPK)-activated protein kinase (MK2 kinase, pMK2), a key mediator of p38-dependent inflammation, in CDI. Exposure of cultured intestinal epithelial cells to the C. difficile toxins TcdA and TcdB resulted in p38-dependent MK2 activation. Toxin-induced IL-8 and GROα release required MK2 activity. We found that p38 and MK2 are activated in response to other actin-disrupting agents, suggesting that toxin-induced cytoskeleton disruption is the trigger for kinase-dependent cytokine response. Phosphorylated MK2 was detected in the intestines of C. difficile-infected hamsters and mice, demonstrating for the first time that the pathway is activated in infected animals. Furthermore, we found that elevated pMK2 correlated with the presence of toxigenic C. difficile among 100 patient stool samples submitted for C. difficile testing. In conclusion, we find that MK2 kinase is activated by TcdA and TcdB and regulates the expression of proinflammatory cytokines. Activation of p38-MK2 in infected animals and humans suggests that this pathway is a key driver of intestinal inflammation in patients with CDI.
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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.