The Mediating Effect Of IL-31/TRPV1 Pathway On DINP-induced Allergic Asthma

Phthalates(PAEs)are widely used in various industrial products,such as various children's toys,food packaging materials,cosmetics,pesticides,medical equipments,clothing and personal care products,and it is one of the most frequently contacted chemicals in human daily life.PAEs are easily spilled from products and enter the body through intaking food and drinking water,and cause various harmful effects such as liver and kidney toxicity,reproductive toxicity and developmental toxicity to humans and animals.Diisononyl phthalate(DINP),as a new type of environmentally friendly plasticizer,has become the most promising plasticizer in PAEs because of its low toxicity.With the deepening of the research on DINP,more and more studies have found that DINP can promote the occurrence and development of allergic asthma,but its underlying mechanism is still unclear.There are relatively few safety data for DINP,especially the very limited studies on DINP dermal exposure.To study the role of plasticizer DINP in allergic asthma and the underlying molecular mechanism.We divided male BALB/c mice into 6 groups,including control group(normal saline),20 mg·kg^-1 DINP group,Ovalbumin(OVA)group,20 mg·kg^-1DINP+OVA group,SB-431542 antagonist group(20 mg·kg^-1DINP+OVA+SB-431542)and CZP antagonist group(20 mg·kg^-1 DINP+OVA+CZP),with ovalbumin(OVA)and hydroxide Aluminum colloids were sensitized and challenged with 1%OVA solution.The exposure period was 28days.Airway hyperresponsiveness(AHR)and lung histopathology(H?E,Masson,PAS)were first performed.Subsequently,ELISA kits were used to detect total Ig E(T-Ig E),OVA-Ig E and OVA-s Ig G1 in serum to evaluate inflammatory factors in the body,and lung tissue homogenate was used to determine pro-inflammatory factors IL-1?,TNF-?,and chemokine OX40L,and the levels of Th1/Th2 immune balance cytokines IL-4,IL-5,IL-13,IL-6 and IFN-?.The expression of IL-31/TRPV1 pathway activation level markers(TRPV1,IL-31)was also observed.The results showed that compared with the normal saline group,the OVA group's lung function,Th2 immune system hyperfunction molecules and various inflammatory factors,and TRPV1/IL-31 pathway activation indexes all increased significantly,and the lung histopathological damage was aggravated.Compared with the OVA group,the lung function,various inflammatory factors,molecules of Th2 immune system hyperfunction,and TRPV1/IL-31 pathway activation indexes also increased significantly in the DINP+OVA group,and the lung histopathological damage was also significantly increased.Compared with the DINP+OVA group,the SB-431542 antagonism group and the CZP antagonism group had obvious reduction in all the indexes.The experimental results show that 20 mg·kg^-1 DINP can aggravate allergic asthma in mice,and IL-31/TRPV1 pathway antagonist SB-431542 and CZP can alleviate the symptoms of allergic asthma and protect the lung tissue of mice.The role of TRPV1/IL-31 pathway may mediate allergic asthma caused by DINP.