Mechanism of indolepropionic acid mediating allergic rhinitis by regulating AKT/T-bet/GZMB/TTP/IL-10 axis

Abstract

Objective: Allergic rhinitis(AR) is one of the most common chronic diseases in the world, which often brings confusion to countless patients. The purpose of this study was to explore whether indolepropionic acid(IPA) intervened AR mice through regulation AKT/T-bet/GZMB/TTP/IL-10 axis alleviates the inflammatory reaction in AR mice and provides a new vision for the treatment of AR. Methods: the AR model of mice was constructed with ovalbumin(OVA), then drug intervention with IPA was performed, and AR symptoms were evaluated on the last day of stimulation, and mouse serum and nasal mucosal tissues were collected for follow-up experiments; the expression levels of immunoglobulin E(IgE), Interleukin(IL)-4, IL-5, IL-10, IL-13 in the serum of mice were detected by Enzyme-linked immunosorbent assay(ELISA); The pathological changes of nasal mucosa were observed by Hematoxylin–eosin(H&E) staining method; The mRNA and protein levels of AKT, T-bet, GZMB, TTP and IL-10 in nasal mucosa were detected by Quantitative reverse transcription PCR (qRT-PCR) and Western Blot. Results: On the last day of stimulation, the score for nasal symptom behavior in the OVA group was more than 5 points, indicating that the model was successfully established. Compared to the OVA group, the nasal symptom behavior score was significantly lower in the OVA + IPA group (P<0.05); The results of HE showed that the inflammatory pathological manifestations of the nasal mucosa in the OVA group were severe, and the inflammatory pathological manifestations of the nasal mucosa in the OVA + IPA group were obviously reduced after treatment; ELISA showed that the levels of IL-4, IL-5, IL-13 and IgE in the OVA group were significantly higher than those in the OVA + IPA group, while the levels of IL-10 were significantly lower than those in the OVA + IPA group (P<0.05); The results of qRT-PCR and Western Blot showed that compared with the OVA group, the mRNA and protein levels of GZMB, IL-10 increased significantly in the nasal mucosa of the OVA + IPA group, but the mRNA levels of AKT, T-bet, TTP decreased significantly (P<0.05). Conclusion: IPA can alleviate the inflammatory response of AR mice by regulating the AKT/T-bet/GZMB/TTP/IL-10 axis.