The role of interleukin-17A in acute paraquat induced lung injury in mice / 中华急诊医学杂志

ABSTRACT

Objective To investigate the role of interleukin-17A (IL-17A) in acute paraquat (PQ)-induced lung injury in mice.Methods A total of 120 healthy SPF grade ICR male mice were randomly (random number) divided into three groups (n =40 in each)normal saline control group (NS),PQ poisoning group (PQ) and antibody neutralization group (PQ + Ab).Mice of PQ group and PQ + Ab group were given 5 mg/mL PQ by one gavage in a dosage of 25 mg/kg body weight,and 5 μg IL-17A neutralizing antibody intra-peritoneally administered immediately after PQ poisoning in PQ + Ab group;Equivalent volume of normal saline instead of PQ was given to mice of NS group.Six survival mice from each group were taken for experiment at 8 h,1 d,3 d,5 d,7 d after PQ poisoningWet to dry ratio (W/D) of lung was determined in mice of each group.HE staining of lung tissue was used to observe the histopathological changes under the light microscope and the pathological scores were graded;Serum interleukin-17A (IL-17A),interleukin-22 (IL-22),interleukin-6 (IL-6),transforming growth factor-β (TGF-β) were detected with enzyme linked immunosorbent assay (ELISA);Expression of interleukin-23 receptor (IL-23R) in lung tissue was determined with immunohistochemical;real-time fluorescence quantification PCR (qRT-PCR) was used to detect the expression of retinoic acid related solitary nuclear receptors' mRNA in lung tissue.Results After administration of PQ,W/D ratio increased (P ＜ 0.01),lung injury was observed in mice of PQ and PQ + Ab groups,levels of cytokines (IL-17A,IL-22,IL-6 and TGF-β) in serum elevated (P ＜0.05),and the expressions of IL-23R mRNA and RORγt mRNA increased (P＜0.01).But in PQ +Ab group,W/D ratio decreased (P ＜0.05),lung injury was alleviated,the levels of cytokines (IL-17A,IL-22,IL-6 and TGF-β) decreased (P ＜ 0.05),and the expressions of IL-23R mRNA and RORγt mRNA reduced (P ＜ 0.05).Conclusions Since IL-17A involves in the lung injury of the mice induced by acute paraquat poisoning,blockade of IL-17A significantly alleviates the acute lung injury in mice.