{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:23:56Z","timestamp":1790760236593,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T00:00:00Z","timestamp":1586476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Human or mouse macrophage cells were treated with lipopolysaccharides (LPS), interferon gamma (IFN\u03b3), or IL-4 alone or concurrently treated with IL-26 to monitor M1 or M2 macrophage subtypes. The expression level of M1 or M2 macrophage genes was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanisms of downstream signaling activation during differentiation were investigated by immunoblotting assay. Our results found that IL-26 promoted macrophage cells from CD80+ M1 macrophage differentiation, not from the CD206+ M2 phenotype. The messenger RNA of M1-type macrophage markers tumor necrosis factor alpha (TNF\u03b1) and inducible nitric oxide synthase (iNOS) was up-regulated in the IL-26-treated group. Also, the M1-related proinflammatory cytokines TNF\u03b1 and IL-6 were induced after IL-26 stimulation. Interestingly, IL-10, a cytokine marker of M2 macrophage, was also elevated after IL-26 stimulation. Moreover, the M1-like macrophage stimulated by IL-26 underwent cJUN, nuclear factor kappa B (NF-\u03baB), and signal transducer and activator of transcription 1 (STAT1) activation. Our findings suggested the role of IL-26 in synovial macrophages of active rheumatoid arthritis and provided a new insight into IL-26 as a candidate therapeutic target in rheumatoid arthritis.<\/jats:p>","DOI":"10.3390\/cells9040938","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T10:41:52Z","timestamp":1586774512000},"page":"938","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and the NF-\u03baB Pathway"],"prefix":"10.3390","volume":"9","author":[{"given":"Yi-Hsuan","family":"Lin","sequence":"first","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hsun","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-2103","authenticated-orcid":false,"given":"Yi-Jen","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Cheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Rheumatology\/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4302-8196","authenticated-orcid":false,"given":"Gu-Jiun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shing-Hwa","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, En Chu Kong Hospital, New Taipei 237, Taiwan"},{"name":"Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huey-Kang","family":"Sytwu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 350, Miaoli County, Taiwan"},{"name":"Department of Microbiology and Immunology, National Defense Medical Center, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Pi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan"},{"name":"Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei 114, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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