ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2012
EP2 and EP4 receptors on muscularis resident macrophages mediate LPS-induced intestinal dysmotility via iNOS upregulation through cAMP/ERK signals.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 41 citations in OpenAlex.
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- Electroacupuncture alleviates ulcerative colitis by targeting CXCL1: evidence from the transcriptome and validation.Frontiers in immunology · 2023Article
- Toward Understanding Wound Immunology for High-Fidelity Skin Regeneration.Cold Spring Harbor perspectives in biology · 2022Review
- Inhibition of Lipopolysaccharide-Induced Inflammatory Signaling by Soft Coral-Derived Prostaglandin AMarine drugs · 2022Article
- Purinergic P2X7 receptor antagonist ameliorates intestinal inflammation in postoperative ileus.The Journal of veterinary medical science · 2022Article
- Crosstalk between epithelium, myeloid and innate lymphoid cells during gut homeostasis and disease.Frontiers in immunology · 2022Review
- Activation of α7nAChR Protects Against Gastric Inflammation and Dysmotility in Parkinson's Disease Rats.Frontiers in pharmacology · 2021Article
- Roles of Macrophages in the Development and Treatment of Gut Inflammation.Frontiers in cell and developmental biology · 2021Review
- Protein kinase A facilitates relaxation of mouse ileum via phosphorylation of neuronal nitric oxide synthase.British journal of pharmacology · 2020Article
- Prostaglandin E2 Regulates Activation of Mouse Peritoneal Macrophages by Staphylococcus aureus through Toll-Like Receptor 2, Toll-Like Receptor 4, and NLRP3 Inflammasome Signaling.Journal of innate immunity · 2020Article
- Neural anti-inflammatory action mediated by two types of acetylcholine receptors in the small intestine.Scientific reports · 2019Article
- The COX-2/prostanoid signaling cascades in seizure disorders.Expert opinion on therapeutic targets · 2019Review
- Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery.World journal of surgery · 2018Article
- The anti-inflammatory pathway regulated via nicotinic acetylcholine receptors in rat intestinal mesothelial cells.The Journal of veterinary medical science · 2017Article
- Therapeutic Action of Honokiol on Postoperative Ileus via Downregulation of iNOS Gene Expression.Inflammation · 2017Article
- Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule.Scientific reports · 2017Article
- The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review).Molecular medicine reports · 2016Review
- A novel coumarin, (+)-3'-angeloxyloxy-4'-keto-3',4'-dihydroseselin, isolated from Bupleurum malconense (Chaihu) inhibited NF-κB activity.Chinese medicine · 2016Article
- Time-dependent changes in inhibitory action of lipopolysaccharide on intestinal motility in rat.The Journal of veterinary medical science · 2015Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal resident macrophages play an important role in gastrointestinal dysmotility by producing prostaglandins (PGs) and nitric oxide (NO) in inflammatory conditions. The causal correlation between PGs and NO in gastrointestinal inflammation has not been elucidated. In this study, we examined the possible role of PGE(2) in the LPS-inducible inducible NO synthase (iNOS) gene expression in murine distal ileal tissue and macrophages. Treatment of ileal tissue with LPS increased the iNOS and cyclooxygenase (COX)-2 gene expression, which lead to intestinal dysmotility. However, LPS did not induce the expression of iNOS and COX-2 in tissue from macrophage colony-stimulating factor-deficient op/op mice, indicating that these genes are expressed in intestinal resident macrophages. iNOS and COX-2 protein were also expressed in dextran-phagocytized macrophages in the muscle layer. CAY10404, a COX-2 inhibitor, diminished LPS-dependent iNOS gene upregulation in wild-type mouse ileal tissue and also in RAW264.7 macrophages, indicating that PGs upregulate iNOS gene expression. EP(2) and EP(4) agonists upregulated iNOS gene expression in ileal tissue and isolated resident macrophages. iNOS mRNA induction mediated by LPS was decreased in the ileum isolated from EP(2) or EP(4) knockout mice. In addition, LPS failed to decrease the motility of EP(2) and EP(4) knockout mice ileum. EP(2)- or EP(4)-mediated iNOS expression was attenuated by KT-5720, a PKA inhibitor and PD-98059, an ERK inhibitor. Forskolin or dibutyryl-cAMP mimics upregulation of iNOS gene expression in macrophages. In conclusion, COX-2-derived PGE(2) induces iNOS expression through cAMP/ERK pathways by activating EP(2) and EP(4) receptors in muscularis macrophages. NO produced in muscularis macrophages induces dysmotility during gastrointestinal inflammation.
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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.