{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:06:09Z","timestamp":1784718369944,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Council of Thailand (NRCT) and Chulalongkorn University","award":["N42A670716"],"award-info":[{"award-number":["N42A670716"]}]},{"name":"Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn University","award":["RA68\/028"],"award-info":[{"award-number":["RA68\/028"]}]},{"name":"Thailand Science research and Innovation Fund Chulalongkorn University","award":["HEAF67300093"],"award-info":[{"award-number":["HEAF67300093"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Inflammation is essential for host defense, but, when dysregulated, it contributes to tissue damage and chronic disease. MicroRNA-146a (miR-146a) is a well-recognized negative regulator of inflammatory signaling, primarily through suppression of the NF-\u03baB pathway; however, its broader proteomic impact under inflammatory conditions remains incompletely defined. In this study, we overexpressed an miR-146a mimic in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and applied quantitative mass spectrometry to characterize global protein abundance changes. Functional overexpression was supported by reduced mRNA abundance of the established miR-146a targets TRAF6 and IRAK1 under LPS-stimulated conditions. Proteomic analysis identified 1232 proteins showing differential abundance under the predefined exploratory criteria, including proteins related to NF-\u03baB activity, inflammasome components, nitric oxide synthesis, and IL-6-associated pathways. Proteins linked to interferon-related signaling were also altered. Targeted validation by quantitative RT-PCR and parallel reaction monitoring supported changes in selected inflammatory mediators, including PTGS2, NOS2, MAPKAPK2, and IRF3. Functionally, miR-146a overexpression was associated with reduced LPS-induced nitric oxide and IL-6 production. Together, these findings provide an exploratory proteomic overview of pathways associated with miR-146a overexpression in activated macrophages and suggest that miR-146a is associated with modulation of multiple inflammatory signaling networks under inflammatory conditions.<\/jats:p>","DOI":"10.3390\/ijms27146514","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:48:28Z","timestamp":1784717308000},"page":"6514","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Global Proteomic Analysis Reveals Inflammatory Pathway Modulation Associated with miR-146a in LPS-Stimulated Macrophages"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3400-3758","authenticated-orcid":false,"given":"Marut","family":"Tangwattanachuleeporn","sequence":"first","affiliation":[{"name":"Faculty of Allied Health Sciences, Burapha University, Chon Buri 20130, Thailand"},{"name":"Research Unit for Sensor Innovation, Burapha University, Chon Buri 20130, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5502-5889","authenticated-orcid":false,"given":"Aunyamon","family":"Srichaimongkol","sequence":"additional","affiliation":[{"name":"Master of Science Program in Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6025-0106","authenticated-orcid":false,"given":"Jiradej","family":"Makjaroen","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sita","family":"Virakul","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9186-2823","authenticated-orcid":false,"given":"Saharat","family":"Nanthawong","sequence":"additional","affiliation":[{"name":"Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3661-4448","authenticated-orcid":false,"given":"H. Sunny","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni Nyoman Ayu","family":"Dewi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Udayana University, Badung 80361, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanapat","family":"Palaga","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thidathip","family":"Wongsurawat","sequence":"additional","affiliation":[{"name":"Division of Medical Bioinformatics, Research Department, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5566-6403","authenticated-orcid":false,"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Research in Inflammation and Immunology (CETRII), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poorichaya","family":"Somparn","sequence":"additional","affiliation":[{"name":"Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s44385-025-00010-4","article-title":"Inflammation: A matter of immune cell life and death","volume":"2","author":"Bender","year":"2025","journal-title":"npj Biomed. 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