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Τετάρτη 4 Αυγούστου 2021

Metabolites of intestinal microflora upregulate microRNA-200c-3p expression level to suppress airway epithelial inflammation via the IL6ST/JNK/STAT3 signaling pathway

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Exp Ther Med. 2021 Sep;22(3):999. doi: 10.3892/etm.2021.10431. Epub 2021 Jul 15.

ABSTRACT

Intestinal microfloras are involved in various types of cancer; however, there is a limited amount of research into the involvement of metabolites of intestinal microflora (MIM) in asthmatic airway epithelial cells (AECs). The present study was designed to reveal the functions and mechanisms of MIM in the asthmatic inflammation of AECs. House dust mite (HDM)-induced asthma cell models were established and treated with mouse MIM. A MTT assay was used to investigate AEC viability, while reverse transcription-quantitative PCR and western blot analysis were used to measure the expression levels of miR-200c-3p, IL6ST, JNK and STAT3 in asthmatic AECs. ELISA was used to measure the concentration of IL-5 and IL-6. Furthermore, the targeting relationship between microRNA(miR)-200c-3p and IL6ST was investigated using a luciferase reporter gene assay. Compar ed with normal human bronchial epithelial cells, HDM-induced AECs had lower expression level of miR-200c-3p, higher mRNA and protein expression levels of IL6ST and an increase in IL-5 and IL-6 concentration. Both MIM and miR-200c-3p mimics suppressed the secretion of IL-5 and L-6 and promoted the proliferation of HDM-induced AECs. MIM could also upregulate miR-200c-3p and downregulate IL6ST and proteins in the JNK/STAT3 pathway. IL6ST was found to be a downstream target of miR-200c-3p. Inhibition of miR-200c-3p reversed the suppression of asthmatic inflammation by MIM. In summary, MIM upregulated miR-200c-3p expression level to reduce the protein and mRNA expression levels of IL6ST and suppress its downstream JNK/STAT3 signaling pathway, therefore inhibiting the asthmatic inflammation of AECs.

PMID:34345281 | PMC:PMC8311286 | DOI:10.3892/etm.2021.10431

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

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