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

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...

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Autores principales: Kimura, Yasuhiro, Shinoda, Masahiro, Shinkai, Masaharu, Kaneko, Takeshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854378/
https://www.ncbi.nlm.nih.gov/pubmed/36684665
http://dx.doi.org/10.7717/peerj.14695
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author Kimura, Yasuhiro
Shinoda, Masahiro
Shinkai, Masaharu
Kaneko, Takeshi
author_facet Kimura, Yasuhiro
Shinoda, Masahiro
Shinkai, Masaharu
Kaneko, Takeshi
author_sort Kimura, Yasuhiro
collection PubMed
description 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.
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spelling pubmed-98543782023-01-21 Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells Kimura, Yasuhiro Shinoda, Masahiro Shinkai, Masaharu Kaneko, Takeshi PeerJ Drugs and Devices 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. PeerJ Inc. 2023-01-17 /pmc/articles/PMC9854378/ /pubmed/36684665 http://dx.doi.org/10.7717/peerj.14695 Text en ©2023 Kimura et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Drugs and Devices
Kimura, Yasuhiro
Shinoda, Masahiro
Shinkai, Masaharu
Kaneko, Takeshi
Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells
title Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells
title_full Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells
title_fullStr Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells
title_full_unstemmed Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells
title_short Solithromycin inhibits IL-13-induced goblet cell hyperplasia and MUC5AC, CLCA1, and ANO1 in human bronchial epithelial cells
title_sort solithromycin inhibits il-13-induced goblet cell hyperplasia and muc5ac, clca1, and ano1 in human bronchial epithelial cells
topic Drugs and Devices
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9854378/
https://www.ncbi.nlm.nih.gov/pubmed/36684665
http://dx.doi.org/10.7717/peerj.14695
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