MyD88 gene knockout attenuates paraquat-induced acute lung injury

•Paraquat poisoning activates the MyD88-dependent pathway causing ALI.•MyD88 gene knockout attenuates paraquat-induced ALI.•MyD88 gene knockout reduces the levels of serum inflammatory cytokines in paraquat poisoning.

ObjectiveThis study investigated the role of myeloid differentiation factor 88 (MyD88) in paraquat-induced acute lung injury (ALI).MethodsC57BL 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-α (TNF-α) and interleukine-1β (IL-1β) 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-α, and IL-1β in the lungs. Immunofluorescence staining was done to evaluate the expression and distribution of MyD88 and nuclear factor κB (NF-κB) in the lungs. Western blotting was conducted to detect the protein level of toll-like receptor (TLR) 4, TLR9, MyD88, and NF-κB in the lungs.ResultsParaquat poisoning significantly increased serum inflammatory cytokines, as well as MyD88, TLR4, TLR9, and NF-κB, and resulted in ALI. After MyD88 KO, the levels of inflammatory cytokines and NF-κB decreased markedly, and ALI was also attenuated although TLR4 and TLR9 expression continued at an elevated level.ConclusionMyD88 mediates paraquat-induced ALI, and MyD88 gene knockout may attenuate paraquat-induced ALI and reduce the production of proinflammatory cytokines.