{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:17:04Z","timestamp":1789877824872,"version":"4.0.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IL-17A, IL-17F, and IL-25 belong to the IL-17 family of cytokines, and are well known to play important roles in the host defense against infection and inflammatory diseases. IL-17C, also a member of the IL-17 family, is highly expressed in the epithelium; however, the function and regulatory mechanism of IL-17C in airway epithelium remain poorly understood. In this study, we demonstrate that polyinosinic\u2013polycytidylic acid (polyI:C), the ligand to Toll-like receptor 3, is a potent inducer of IL-17C mRNA and protein expression in primary normal human bronchial epithelial (NHBE) cells. IL-17C induction by polyI:C was both time dependent and dose dependent, and was attenuated by inhibitors of the Toll-IL-1 receptor domain\u2013containing adaptor\u2013inducing INF-\u03b2 (TRIF)\u2013NF-\u03baB pathway, Pepinh-TRIF, BAY11, NF-\u03baB inhibitor III, and NF-\u03baB p65 small interfering RNA, suggesting that IL-17C expression is induced by polyI:C via the Toll-like receptor 3\u2013TRIF\u2013NF-\u03baB pathway. Both IL-17C and polyI:C increased the expression of antimicrobial peptides and proinflammatory cytokines, such as human \u03b2-defensin (hBD) 2, colony-stimulating factor 3 (CSF3), and S100A12 in NHBE cells. Knockdown of IL-17 receptor (IL-17R) E, the specific receptor for IL-17C, using IL-17RE small interfering RNA, attenuated polyI:C-induced hBD2, CSF3, and S100A12 expression, without any reduction of polyI:C-induced IL-17C expression, which suggest that IL-17C enhances hBD2, CSF, and S100A12 expression in an autocrine\/paracrine manner in NHBE cells. Knockdown of IL-17C also decreased polyI:C-induced hBD2, CSF3, and S100A12 expression. Thus, our data demonstrate that IL-17C is an essential epithelial cell\u2013derived cytokine that enhances mucosal host defense responses in a unique autocrine\/paracrine manner in the airway epithelium.<\/jats:p>","DOI":"10.1165\/rcmb.2013-0130oc","type":"journal-article","created":{"date-parts":[[2013,8,14]],"date-time":"2013-08-14T12:14:49Z","timestamp":1376482489000},"page":"30-39","source":"Crossref","is-referenced-by-count":59,"title":["Toll-Like Receptor\u2013Mediated Airway IL-17C Enhances Epithelial Host Defense in an Autocrine\/Paracrine Manner"],"prefix":"10.1093","volume":"50","author":[{"given":"Hideki","family":"Kusagaya","sequence":"first","affiliation":[{"name":"Second Division, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Second Division, Department of Internal Medicine"},{"name":"Department of Laboratory Medicine, 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