C-C Motif Chemokine Receptor 3-Mediated Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase Signaling: Promising Targets for Human Airway Epithelial Mucin 5AC Induction by Eotaxin-2 and Eotaxin-3.

Autor:	Jo S; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea, jhsy8549@gmail.com., Na HG; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea., Choi YS; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea., Bae CH; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea., Song SY; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea., Kim YD; Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.; Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea.
Jazyk:	angličtina
Zdroj:	International archives of allergy and immunology [Int Arch Allergy Immunol] 2023; Vol. 184 (9), pp. 893-902. Date of Electronic Publication: 2023 Aug 08.
DOI:	10.1159/000531911
Abstrakt:	Introduction: Eotaxin-2 and -3 of the C-C chemokine subfamily function as potent chemoattractant factors for eosinophil recruitment and various immune responses in allergic and inflammatory airway diseases. Mucin 5AC (MUC5AC), a major gel-forming secretory mucin, is overexpressed in airway inflammation. However, the association between mucin secretion and eotaxin-2/3 expression in the upper and lower airway epithelial cells has not been fully elucidated. Therefore, in this study, we investigated the effects of eotaxin-2/3 on MUC5AC expression and its potential signaling mediators. Methods: We analyzed the effects of eotaxin-2 and -3 on NCI-H292 human airway epithelial cells and primary human nasal epithelial cells (HNEpCs) via reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Along with immunoblot analyses with specific inhibitors and small interfering RNA (siRNA), we explored the signaling pathway involved in MUC5AC expression following eotaxin-2/3 treatment. Results: In HCI-H292 cells, eotaxin-2/3 activated the mRNA expression and protein production of MUC5AC. A specific inhibitor of C-C motif chemokine receptor 3 (CCR3), SB328437, suppressed eotaxin-2/3-induced MUC5AC expression at both the mRNA and protein levels. Eotaxin-2/3 induced the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2 and p38, whereas pretreatment with a CCR3 inhibitor significantly attenuated this effect. Induction of MUC5AC expression with eotaxin-2/3 was decreased by U0126 and SB203580, specific inhibitors of ERK1/2 and p38 mitogen-activated protein kinase (MAPK), respectively. In addition, cell transfection with ERK1/2 and p38 siRNAs inhibited eotaxin-2/3-induced MUC5AC expression. Moreover, specific inhibitors (SB328437, U0126, and SB203580) attenuated eotaxin-2/3-induced MUC5AC expression in HNEpCs. Conclusion: Our results imply that CCR3-mediated ERK1/2 and p38 MAPK are involved in the signal transduction of eotaxin-2/3-induced MUC5AC overexpression. (© 2023 The Author(s). Published by S. Karger AG, Basel.)
Databáze:	MEDLINE
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