Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells

• Published in: PeerJ Vol. 11; p. e14695
• Main Authors: Kimura, Yasuhiro, Shinoda, Masahiro, Shinkai, Masaharu, Kaneko, Takeshi
• Format: Journal Article
• Language: English
• Published: United States PeerJ 17.01.2023; PeerJ. Ltd; PeerJ, Inc; PeerJ Inc
• Subjects: Acids; Analysis; Anoctamin-1; Anoctamin-1 - genetics; Antibiotics; Asthma; Biology (General); Chloride channel accessory 1; Chloride Channels; Chloride channels (calcium-gated); Chloride Channels - genetics; Drugs and Devices; Epithelial cells; ETS protein; Gene expression; Goblet cell; Goblet Cells; Goblet Cells - drug effects; Goblet Cells - pathology; Humans; Hyperplasia; Interleukin 13; Interleukin-13 - genetics; Interleukins; Kinases; Macrolide antibiotics; Macrolides; Macrolides - pharmacology; Medicine; Microscopy; Molecular modelling; MUC5AC; Mucin; Mucin 5AC; Mucin 5AC - genetics; Mucins; Neoplasm Proteins; Neoplasm Proteins - metabolism; Phosphorylation; Protein expression; Proteins; QH301-705.5; R; Respiratory Medicine; RNA; RNA, Messenger; RNA, Messenger - genetics; SAM pointed domain containing ETS transcription factor; Solithromycin; Stat6 protein; Japan; Goblet cell; Anoctamin-1; Mucin; Solithromycin; SAM pointed domain containing ETS transcription factor; Chloride channel accessory 1; MUC5AC
• DOI: 10.7717/peerj.14695
• ISSN: 2167-8359

Solithromycin is a novel fluoroketolide antibiotic belonging to the class of macrolide antibiotics. Activation of the interleukin (IL)-13 receptor leads to STAT6 activation and subsequent induction of SAM pointed domain containing ETS transcription factor (SPDEF), chloride channel accessory 1 (CLCA1), and anoctamin-1 (ANO1), all of which are associated with the induction of MUC5AC. We examined the effects of solithromycin on mucin production led by IL-13 signaling. Normal human bronchial epithelial cells were grown at the air-liquid interface with IL-13 with/without solithromycin for 14 days. Histochemical analysis was performed using hematoxylin and eosin staining and MUC5AC immunostaining. MUC5AC , SPDEF , CLCA1 , and ANO1 mRNA expressions were examined using real-time polymerase chain reaction. Western blot analysis was performed to assess CLCA1 and ANO1 proteins, and phosphorylation of STAT6 and ERK. Solithromycin attenuated IL-13 induction of goblet cell hyperplasia and MUC5AC , CLCA1 and ANO1 mRNA and protein expression induced by IL-13, but had no effect on the phosphorylation of STAT6 and ERK. Our results indicate that solithromycin could attenuate goblet cell hyperplasia and MUC5AC induced by IL-13 through inhibition of CLCA1 and ANO1 mRNA and protein expression. However, much more information is required to clarify the molecular mechanisms underlying the inhibition of CLCA1 and ANO1 by solithromycin.