Peroxisome Proliferator Activated Receptor Gamma(PPAP?) Agonist Rosiglitazone Ameliorate Airway Inflammation By Inhibiting TLR2/NLRP3 Inflammatory Pathway In Asthmatic Mice

Background Bronchial asthma is a heterogeneous disease characterized by a variety of cellular and cellular components involved in chronic inflammation of the airways,and is a type I allergic disease.According to the World Health Organization,about 300 million people worldwide suffer from asthma,and the morbidity and mortality of asthma are still high,which seriously threatens human health.Studies have shown that TLR2 is a type I transmembrane protein,NLRP3 is a cytoplasmic receptor,and the TLR2/NLRP3 inflammatory pathway is involved in the regulation of asthma.PPAR? is an important nuclear transcription factor involved in the transcriptional regulation of a variety of cell and tissue pathophysiology,restricting the metabolism of glucose and lipids.Rosiglitazone is a specific PPAR gamma receptor agonist with potential asthma therapeutic effects.Although PPAR? activation is thought to have an inhibitory effect on airway inflammation in asthma,the exact mechanism remains unclear.Therefore,this study was to construct a C57 mouse acute asthma model to explore the possible mechanism of PPAR? in the acute asthma regulated by TLR2/NLRP3 inflammatory pathway under the intervention of PPAR? agonist rosiglitazone.Objective The purpose of this study was to explore the function and mechanism of peroxisome proliferator activated receptor gamma agonist in the toll-like receptor 2(TLR2)/nod-like receptor with pyrin domain containing 3(NLRP3)inflammatory corpuscle pathway of asthmatic mice.Methods Twenty-four female mice(C57)were randomly divided into 4 groups: the control group,the asthma model group challenged by ovalbumin(OVA),the PPAR ? agonist rosiglitazone treatment group,and the rosiglitazone group.The intervention group and the asthma group were sensitized and challenged with ovalbumin(OVA)to construct a mouse asthma model.The intervention group inhaled rosiglitazone solution before aerosol inhalation of OVA.Determination of IL-4 and IL-13 in BALF by enzyme-linked immunosorbent assay(ELISA).The infiltration of peribronchial inflammatory cells as well as the proliferation and mucus secretion of bronchial epithelial goblet cells were observed by hematoxylin and eosin and periodic acid-Schiff staining.Western blots were employed to detect the expression levels of TLR2,PPAR?,NF-?B,NLRP3,and ASC.Results The number of inflammatory cells and eosinophils,interleukin-4(IL-4),and IL-13 were significantly higher in the C57 asthma group compared to the C57 control group and the treatment group(P<0.05),while the eosinophils,IL-4 and IL-13 in the rosiglitazone group showed no significant changes compared with the control group(p > 0.05)..The infiltration of peribronchiolar inflammatory cells,wall thickening,goblet cell hyperplasia,and mucus secretion in the treatment group were all significantly decreased compared to those in the asthma group.PPAR? expression in the treatment group was significantly higher compared to the asthma group and the control group(P<0.05).The protein expression levels of TLR2,NF-?B,NLRP3 and ASC in rosiglitazone group were close to those in the control group(P>0.05).The protein expression levels of TLR2,NF-kappa B,NLRP3,and ASC were significantly lower compared to the asthma group but were higher compared to the control group(P<0.05).Conclusions PPAR? Agonist rosiglitazone ameliorates airway inflammation by inhibiting the activation of TLR2/NLRP3 inflammatory corpuscles pathway.