The role of interleukin-17A in acute paraquat induced lung injury in mice

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 poisoning: Wet 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. Key words: Paraquat; Interleukin-17A; Mice; Acute lung injury; Th17 cell