MyD88 gene knockout attenuates paraquat-induced acute lung injury

Abstract

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 48h 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.