{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:09:58Z","timestamp":1774976998916,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K09829"],"award-info":[{"award-number":["21K09829"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gingival epithelial cells (GECs) are physical and immunological barriers against outward pathogens while coping with a plethora of non\u2010pathogenic commensal bacteria. GECs express several members of Toll\u2010like receptors (TLRs) and control subsequent innate immune responses. TLR4 senses lipopolysaccharide (LPS) while TLR7\/8 recognizes single\u2010strand RNA (ssRNA) playing important roles against viral infection. However, their distinct roles in GECs have not been fully demonstrated. Here, we analyzed biological responses of GECs to \u00a0LPS\u00a0and CL075, a TLR7\/8 agonist. GE1, a mouse gingival epithelial cell line, constitutively express TLR4 and TLR7, but not TLR8, like primary skin keratinocytes. Stimulation of GE1 cells with CL075 induced cytokine, chemokine, and antimicrobial peptide \u00a0expressions, the pattern of which is rather different from that with LPS: higher mRNA levels of interferon (IFN) \u03b2, CXCL10, and \u03b2\u2010defensin (BD) 14 (mouse homolog of human BD3); lower levels of tumor necrosis factor (TNF), CCL5, CCL11, CCL20, CXCL2, and CX3CL1. As for the intracellular signal transduction of GE1 cells, CL075 rapidly induced significant AKT phosphorylation but failed to activate IKK\u03b1\/\u03b2\u2010NF\u03baB pathway, whereas LPS induced marked IKK\u03b1\/\u03b2\u2010NF\u03baB activation without significant AKT phosphorylation. In contrast, both CL075 and LPS induced rapid IKK\u03b1\/\u03b2\u2010NF\u03baB activation and AKT phosphorylation in a macrophage cell line. Furthermore, specific inhibition of AKT activity abrogated CL075\u2010induced IFN\u03b2, CXCL10, and BD14 mRNA expression in GE1 cells. Thus, TLR4\/7 ligands appear to induce rather different host\u2010defense responses of GECs through distinct intracellular signaling mechanisms.<\/jats:p>","DOI":"10.1002\/jcb.30576","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T09:14:40Z","timestamp":1715332480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["TLR4\/7\u2010mediated host\u2010defense responses of gingival epithelial cells"],"prefix":"10.1002","volume":"125","author":[{"given":"Norika","family":"Chiba","sequence":"first","affiliation":[{"name":"Department of Oral Biochemistry Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryohei","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"},{"name":"Department of Oral and Maxillofacial Surgery Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomokazu","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-1544","authenticated-orcid":false,"given":"Tetsuya","family":"Matsuguchi","sequence":"additional","affiliation":[{"name":"Department of Oral Biochemistry Kagoshima University Graduate School of Medical and Dental Sciences Kagoshima 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