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In this study, we evaluated whether receptor\u2010interacting protein kinase 2 (Ripk2), an adaptor protein of the cytosolic receptors nucleotide\u2010binding oligomerization domain (NOD)1 and NOD2, in macrophages and human decidual stromal cells (hDSCs) contributes to immune responses against <jats:italic>F. nucleatum<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of Study<\/jats:title><jats:p>Bone marrow\u2010derived macrophages (BMDMs) isolated from wild\u2010type (WT) and Ripk2\u2010deficient mice and hDSCs were cultured with <jats:italic>F. nucleatum<\/jats:italic> (MOI 1, 10, 100). BMDMs and hDSCs were assessed using enzyme\u2010linked immunosorbent assay, Western blot analysis, real\u2010time PCR, and nitrite assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Fusobacterium nucleatum<\/jats:italic>\u2010induced production of IL\u20106, but not of TNF\u2010\u03b1 and IL\u201010, was lower in Ripk2\u2010deficient BMDMs than in WT cells. Western blotting revealed a decrease in <jats:italic>F. nucleatum<\/jats:italic>\u2010induced p65 phosphorylation in Ripk2\u2010deficient macrophages, whereas mitogen\u2010activated protein kinases activation was comparable between WT and Ripk2\u2010deficient cells. The production of nitric oxide (NO) in response to <jats:italic>F. nucleatum<\/jats:italic> and the gene and protein expression of inducible NO synthase was impaired in Ripk2\u2010deficient BMDMs. In hDSCs, <jats:italic>F. nucleatum<\/jats:italic> upregulated the gene and protein expression of NOD1, NOD2, and Ripk2 in a time\u2010dependent manner. <jats:italic>F. nucleatum<\/jats:italic> also increased the production of IL\u20106, CXCL8, and CCL2, whereas this production was decreased by the Ripk2 inhibitors SB203580 and PP2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In conclusion, Ripk2 signaling appears to contribute to the <jats:italic>F. nucleatum<\/jats:italic>\u2010induced immune response and can be a preventive and therapeutic target against APOs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13403","type":"journal-article","created":{"date-parts":[[2021,2,13]],"date-time":"2021-02-13T04:42:07Z","timestamp":1613191327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Receptor\u2010interacting protein kinase 2 contributes to host innate immune responses against <i>Fusobacterium nucleatum<\/i> in macrophages and decidual stromal cells"],"prefix":"10.1111","volume":"86","author":[{"given":"Ji\u2010Yeon","family":"Park","sequence":"first","affiliation":[{"name":"Laboratory Animal Medicine College of Veterinary Medicine Chonnam National University  Gwangju Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tae\u2010Sung","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory Animal Medicine College of Veterinary Medicine Chonnam National University  Gwangju Republic of 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