Protective effect of miR-138-5p inhibition modified human mesenchymal stem cell on ovalbumin-induced allergic rhinitis and asthma syndrome.

Abstract

The objective of the study is to evaluate the protective effects of human mesenchymal stem cells (hMSCs) modified with miR‐138‐5p inhibitor against the allergic rhinitis and asthma syndrome (ARAS). MiR‐138‐5p or negative control was transfected into hMSCs, and fluorescence‐activated cell sorting was used to evaluate hMSC surface markers. Quantitative real‐time PCR (qRT‐PCR) was used to evaluate miR‐138‐5p, SIRT1, caspase‐3, IL‐6, IL‐1β and TNF‐α levels after TNF‐α and IL‐6 stimulations. hMSCs with or without miR‐138‐5p inhibition was intranasally administered into ARAS mice (n = 10 each group), followed by monitoring sneezing and nasal rubbing events to evaluate the allergic symptoms. Histamine, ovalbumin‐specific IgE, IgG2a, IgG1 and LTC4 release were monitored in the serum and nasal lavage fluid using enzyme‐linked immunosorbent assay. Expression of SIRT1 and HMGB1/TLR4 pathway in nasal mucosa was assessed. After miR‐138‐5p inhibitor transfection, the hMSC lineage was preserved. Binding between SIRT1 and miR‐138‐4p was observed, and miR‐138‐5p inhibition led to upregulation of SIRT1. Inhibition of miR‐138‐5p led to attenuated inflammatory responses of hMSCs upon TNF‐α and IL‐6 stimulation, and allergic symptoms in mice, as well as histamine and ovalbumin‐specific IgG release. hMSCs with miR‐138‐5p inhibition showed characteristics of activated SIRT1 and inhibited HMGB1/TLR4 pathway. Inhibition of miR‐138‐5p in hMSCs enhanced its effects in attenuating inflammatory responses and allergic reaction in the ARAS model, which is presumably regulated by SIRT1 and the HMGB1/TLR4 pathway.