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

by Selleckchem | Oct 10 2023

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.

Comments:

Based on the provided information, it appears that the study investigated the effects of solithromycin, a novel fluoroketolide antibiotic, on mucin production induced by IL-13 signaling in normal human bronchial epithelial cells. The researchers aimed to understand the molecular mechanisms underlying the inhibition of certain genes and proteins involved in mucin production.

The IL-13 receptor activates STAT6, which leads to the induction of several genes, including SAM pointed domain containing ETS transcription factor (SPDEF), chloride channel accessory 1 (CLCA1), and anoctamin-1 (ANO1). These genes are associated with the production of MUC5AC, a type of mucin. Goblet cell hyperplasia, characterized by an increase in goblet cells that produce and secrete mucin, is a hallmark of certain respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD).

In this study, the researchers grew normal human bronchial epithelial cells at the air-liquid interface and exposed them to IL-13, either with or without solithromycin, for 14 days. They performed histochemical analysis using hematoxylin and eosin staining to visualize the tissue structure, as well as MUC5AC immunostaining to detect the presence of MUC5AC.

To assess the effects of solithromycin on gene expression, real-time polymerase chain reaction (PCR) was used to measure the mRNA levels of MUC5AC, SPDEF, CLCA1, and ANO1. Additionally, Western blot analysis was performed to assess the protein levels of CLCA1 and ANO1, as well as the phosphorylation status of STAT6 and ERK, which are signaling proteins involved in IL-13 signaling.

The results of the study demonstrated that solithromycin attenuated the induction of goblet cell hyperplasia and the expression of MUC5AC, CLCA1, and ANO1 at both the mRNA and protein levels induced by IL-13. However, solithromycin did not affect the phosphorylation of STAT6 and ERK, suggesting that its mechanism of action in inhibiting mucin production may be independent of these signaling pathways.

The findings suggest that solithromycin has the potential to reduce goblet cell hyperplasia and MUC5AC production induced by IL-13. However, the study acknowledges that more research is needed to fully understand the molecular mechanisms underlying the inhibitory effects of solithromycin on CLCA1 and ANO1, the genes associated with chloride channel regulation and mucin production.

It's important to note that this information is based on the provided text and may not encompass the entirety of the research conducted on solithromycin's effects on IL-13-induced mucin production. For comprehensive and up-to-date information, referring to the original research article or consulting with a medical professional or researcher would be advisable.