ArticleInfection and immunity2007
p38 mitogen-activated protein kinase controls NF-kappaB transcriptional activation and tumor necrosis factor alpha production through RelA phosphorylation mediated by mitogen- and stress-activated protein kinase 1 in response to Borrelia burgdorferi antigens.
Article in Infection and immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Exploring the Effectiveness and Potential Pharmacological Mechanism of Minocycline for Spinal Cord Injury through Meta-Analysis and Network Pharmacology.Current neuropharmacology · 2025Pooled it
- Systematic review of p38 mitogen-activated kinase and its functional role in reproductive tissues.American journal of reproductive immunology (New York, N.Y. : 1989) · 2018Pooled it
- Antioxidant and Immunostimulatory Effects of Lactobacillus Strains in RAW 264.7 Macrophages via NF-κB and MAPK Signaling Pathways.Probiotics and antimicrobial proteins · 2026Article
- MSK1 Downstream Signaling Contributes to Inflammatory Pain in the Superficial Spinal Dorsal Horn.International journal of molecular sciences · 2025Article
- Heat-Induced Pathophysiological and Metabolic Changes at the Feto-Maternal Interface Predisposing to Preterm Birth.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Intravenously injected poly(amino acid) nanoformulation relieves spinal cord injury through synergistical modulation of microenvironments.Materials today. Bio · 2025Article
- Mesenchymal stem cells suppress NF-κB and ERK signalling while enhancing chemotaxis in CD4Scientific reports · 2025Article
- Ulcerative colitis: the healing power of macrophages.Tissue barriers · 2025Review
- Probiotic Characteristics and the Anti-Inflammatory Effects ofMicroorganisms · 2024Article
- The emerging role of irisin in experimentally induced arthritis: a recent update involving HMGB1/MCP1/Chitotriosidase I-mediated necroptosis.Redox report : communications in free radical research · 2022Article
- Immunostimulatory Activity of Lactic Acid Bacteria Cell-Free Supernatants through the Activation of NF-κB and MAPK Signaling Pathways in RAW 264.7 Cells.Microorganisms · 2022Article
- Hepatocyte DAX1 Deletion Exacerbates Inflammatory Liver Injury by Inducing the Recruitment of CD4International journal of molecular sciences · 2022Article
- Methylsulfonylmethane ameliorates inflammation via NF-κB and ERK/JNK-MAPK signaling pathway in chicken trachea and HD11 cells during Mycoplasma gallisepticum infection.Poultry science · 2022Article
- Innate Immune Training of Human Macrophages by Cathelicidin Analogs.Frontiers in immunology · 2022Article
- Flavonols and Flavones as Potential anti-Inflammatory, Antioxidant, and Antibacterial Compounds.Oxidative medicine and cellular longevity · 2022Review
- Palmitic acid induces intestinal lipid metabolism disorder, endoplasmic reticulum stress and inflammation by affecting phosphatidylethanolamine content in large yellow croakerFrontiers in immunology · 2022Article
- Article
- Monocyte-released HERV-K dUTPase engages TLR4 and MCAM causing endothelial mesenchymal transition.JCI insight · 2021Article
- Fibroblast Growth Factor Type 1 Ameliorates High-Glucose-Induced Oxidative Stress and Neuroinflammation in Retinal Pigment Epithelial Cells and a Streptozotocin-Induced Diabetic Rat Model.International journal of molecular sciences · 2021Article
- Non-toxic sulfur inhibits LPS-induced inflammation by regulating TLR-4 and JAK2/STAT3 through IL-6 signaling.Molecular medicine reports · 2021Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The interaction of Borrelia burgdorferi, the causative agent of Lyme borreliosis, with phagocytic cells induces the activation of NF-kappaB and the expression of proinflammatory cytokines including tumor necrosis factor alpha (TNF-alpha). B. burgdorferi-induced TNF-alpha production is also dependent on the activation of p38 mitogen-activated protein (MAP) kinase. The specific contribution of these signaling pathways to the response of phagocytic cells to the spirochete and the molecular mechanisms underlying this response remain unresolved. We now show that p38 MAP kinase activity regulates the transcriptional activation of NF-kappaB in response to spirochetal lysate stimulation of phagocytic cells. The regulation occurs at the nuclear level and is independent of the translocation of the transcription factor to the nucleus or its capacity to bind to specific DNA target sequences. In RAW264.7 cells, p38alpha MAP kinase regulates the phosphorylation of NF-kappaB RelA. p38 MAP kinase phosphorylates the nuclear kinase mitogen- and stress-activated protein kinase 1 (MSK1). MSK1 in turn phosphorylates the transcriptionally active subunit of NF-kappaB, RelA. The repression of MSK1 expression with small interfering RNA results in reduced RelA phosphorylation and a significant decrease in the production of TNF-alpha in response to B. burgdorferi lysates. Overall, these results clarify the contribution of the signaling pathways that are activated in response to the interaction of spirochetes with phagocytic cells to TNF-alpha production. Our results situate p38 MAP kinase activity as a central regulator of the phagocytic proinflammatory response through MSK1-mediated transcriptional activation of the transcription factor NF-kappaB.
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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.