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Immunol."],"abstract":"<jats:p>Lipoteichoic acid (LTA) and peptidoglycan (PGN) are considered as key virulence factors of <jats:italic>Staphylococcus aureus<\/jats:italic>, which is a representative sepsis-causing Gram-positive pathogen. However, cooperative effect of <jats:italic>S. aureus<\/jats:italic> LTA and PGN on nitric oxide (NO) production is still unclear despite the pivotal roles of NO in initiation and progression of sepsis. We here evaluated the cooperative effects of <jats:italic>S. aureus<\/jats:italic> LTA (SaLTA) and muramyl dipeptide (MDP), the minimal structure of PGN, on NO production in both a mouse macrophage-like cell line, RAW 264.7 and mouse bone marrow-derived macrophages (BMMs). Although MDP alone did not affect NO production, MDP potently enhanced SaLTA-induced NO production via the expression of inducible NO synthases. The enhanced NO production was ameliorated in BMMs from TLR2-, CD14-, MyD88-, and NOD2-deficient mice. Moreover, the augmented SaLTA-induced NO production by MDP was attenuated by inhibitors specific for PAFR and MAP kinases. Furthermore, MDP also potently increased SaLTA-induced activities of STAT1, NF-\u03baB, and AP-1 transcription factors, and specific inhibitors for these transcription factors suppressed the elevated NO production. Collectively, these results demonstrated that MDP potentiates SaLTA-induced NO production via TLR2\/NOD2\/PAFR, MAP kinases signaling axis, resulting in the activation of NF-\u03baB, AP-1 and STAT1 transcription factors.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1451315","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T06:51:01Z","timestamp":1733467861000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Muramyl dipeptide potentiates Staphylococcus aureus lipoteichoic acid-induced nitric oxide production via TLR2\/NOD2\/PAFR signaling pathways"],"prefix":"10.3389","volume":"15","author":[{"given":"Jintaek","family":"Im","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun 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