Increased Interleukin-17C Production by the Toll-Like Receptor 3 Ligand Poly(I:C) in Primary Cystic Fibrosis Airway Epithelial Cells
Abstract
Cystic fibrosis (CF) airway disease is characterized by exaggerated inflammatory responses and progressive respiratory failure. Although interleukin-8 (IL-8) is a central mediator of neutrophilic inflammation in the CF airway, the upstream epithelial pathways that regulate cytokine production remain incompletely understood. Interleukin-17C (IL-17C) is an epithelial-derived IL-17 family cytokine that can promote inflammatory signaling in an autocrine/paracrine manner, but its regulation in CF-derived airway epithelial cells remains poorly defined. Here, we examined Toll-like receptor (TLR) ligand-induced IL-17C regulation in primary human airway epithelial cells derived from bronchial and small airway compartments, including normal human bronchial epithelial cells, CF-derived human bronchial epithelial cells, small airway epithelial cells (SAEC), and CF-derived SAEC (D-SAEC-CF). Among the ligands tested, polyinosinic-polycytidylic acid [poly(I:C)], a synthetic TLR3 ligand, consistently revealed differences in IL-17C and IL-8 induction between non-CF and CF-derived cells in both epithelial cell systems. Time-course analyses showed that poly(I:C)-induced IL-17C expression increased gradually and exhibited relatively delayed kinetics compared with the rapid interferon-β response, resembling IL-8 induction. Pharmacological inhibition indicated that c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB, but not extracellular signal-regulated kinase, were involved in poly(I:C)-induced IL-17C expression. Basal TLR3 and IL-17RE mRNA levels were elevated most clearly in D-SAEC-CF cells; however, IL-17RE knockdown did not significantly reduce poly(I:C)-induced IL-8 production in bronchial epithelial cells. Together, these findings suggest that poly(I:C)-induced IL-17C production may represent a TLR3-dependent epithelial inflammatory response in CF-derived primary airway epithelial cells.
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BibTeX
@article{uenoshuto2026increased,
title = {{Increased Interleukin-17C Production by the Toll-Like Receptor 3 Ligand Poly(I:C) in Primary Cystic Fibrosis Airway Epithelial Cells}},
author = {Keiko Ueno-Shuto and Megumi Hayashi and Yukihiro Tasaki and Shunsuke Kamei and Kouhei Onuki and Mary Ann Suico and Hirofumi Kai and Tsuyoshi Shuto},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = jul,
doi = {10.1248/bpb.b26-00266},
url = {https://www.jstage.jst.go.jp/article/bpb/49/7/49_b26-00266/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Increased Interleukin-17C Production by the Toll-Like Receptor 3 Ligand Poly(I:C) in Primary Cystic Fibrosis Airway Epithelial Cells
AU - Keiko Ueno-Shuto
AU - Megumi Hayashi
AU - Yukihiro Tasaki
AU - Shunsuke Kamei
AU - Kouhei Onuki
AU - Mary Ann Suico
AU - Hirofumi Kai
AU - Tsuyoshi Shuto
PY - 2026
DA - 2026/07/28
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b26-00266
UR - https://www.jstage.jst.go.jp/article/bpb/49/7/49_b26-00266/_article
AB - Cystic fibrosis (CF) airway disease is characterized by exaggerated inflammatory responses and progressive respiratory failure. Although interleukin-8 (IL-8) is a central mediator of neutrophilic inflammation in the CF airway, the upstream epithelial pathways that regulate cytokine production remain incompletely understood. Interleukin-17C (IL-17C) is an epithelial-derived IL-17 family cytokine that can promote inflammatory signaling in an autocrine/paracrine manner, but its regulation in CF-derived airway epithelial cells remains poorly defined. Here, we examined Toll-like receptor (TLR) ligand-induced IL-17C regulation in primary human airway epithelial cells derived from bronchial and small airway compartments, including normal human bronchial epithelial cells, CF-derived human bronchial epithelial cells, small airway epithelial cells (SAEC), and CF-derived SAEC (D-SAEC-CF). Among the ligands tested, polyinosinic-polycytidylic acid [poly(I:C)], a synthetic TLR3 ligand, consistently revealed differences in IL-17C and IL-8 induction between non-CF and CF-derived cells in both epithelial cell systems. Time-course analyses showed that poly(I:C)-induced IL-17C expression increased gradually and exhibited relatively delayed kinetics compared with the rapid interferon-β response, resembling IL-8 induction. Pharmacological inhibition indicated that c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB, but not extracellular signal-regulated kinase, were involved in poly(I:C)-induced IL-17C expression. Basal TLR3 and IL-17RE mRNA levels were elevated most clearly in D-SAEC-CF cells; however, IL-17RE knockdown did not significantly reduce poly(I:C)-induced IL-8 production in bronchial epithelial cells. Together, these findings suggest that poly(I:C)-induced IL-17C production may represent a TLR3-dependent epithelial inflammatory response in CF-derived primary airway epithelial cells.
SN - 1347-5215
SN - 0918-6158
ER -