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

PeerJ. 2023 Jan 17:11:e14695. doi: 10.7717/peerj.14695. eCollection 2023.

Abstract

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.

Keywords: Anoctamin-1; Chloride channel accessory 1; Goblet cell; MUC5AC; Mucin; SAM pointed domain containing ETS transcription factor; Solithromycin.

MeSH terms

  • Anoctamin-1 / genetics
  • Chloride Channels / genetics
  • Goblet Cells* / drug effects
  • Goblet Cells* / pathology
  • Humans
  • Hyperplasia
  • Interleukin-13* / genetics
  • Macrolides* / pharmacology
  • Mucin 5AC / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / genetics

Substances

  • ANO1 protein, human
  • Anoctamin-1
  • Chloride Channels
  • CLCA1 protein, human
  • Interleukin-13
  • Macrolides
  • MUC5AC protein, human
  • Mucin 5AC
  • Neoplasm Proteins
  • RNA, Messenger
  • solithromycin

Grants and funding

This research was supported by a Grant-in-Aid for Scientific Research (KAKENHI) No. 15K09183 for Masaharu Shinkai and the Yokohama City University Research Fund for Masaharu Shinkai and Takeshi Kaneko. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.