MyD88 gene knockout attenuates paraquat-induced acute lung injury

Objective: This study investigated the role of myeloid differentiation factor 88 (MyD88) in paraquatinduced acute lung injury (ALI). Methods: C57BL mice were divided into the control group, paraquat group, MyD88 knockout (KO) group, and MyD88 KO plus paraquat group. At 48 h after paraquat poisoning, serum and lung tissues were collected. ELISA was employed to detect tumor necrosis factor-alpha (TNF-alpha) and interleukine-1 beta (IL-1 beta contents in serum. Lung tissues were processed for hematoxylin-eosin staining, followed by histological scoring. PCR was performed to detect the mRNA expression of MyD88, TNF-alpha, and IL-1 beta in the lungs. Immunofluorescence staining was done to evaluate the expression and distribution of MyD88 and nuclear factor KB (NF-kappa B) in the lungs. Western blotting was conducted to detect the protein level of toll like receptor (TLR) 4, TLR9, MyD88, and NF-kappa B in the lungs. Results: Paraquat poisoning significantly increased serum inflammatory cytokines, as well as MyD88, TLR4, TLR9, and NF-kappa B, and resulted in ALI. After MyD88 KO, the levels of inflammatory cytokines and NF-kappa B decreased markedly, and ALI was also attenuated although TLR4 and TLR9 expression continued at an elevated level. Conclusion: MyD88 mediates paraquat-induced ALI, and MyD88 gene knockout may attenuate paraquatinduced ALI and reduce the production of proinflammatory cytokines. (C) 2017 Elsevier B.V. All rights reserved.