ABSTRACT
AIM: To observe the effect and possible mechanism of stimulation of Yes-associated protein (YAP) activity on acute lung injury and repair induced by LPS in mice. METHODS: Ninety adult male ICR mice were divided into two groups: acute lung injury model group induced by LPS (7.5 mg/kg, i.p.) and LPS+XMU treatment (1 mg•kg-1•d-1) group. At 0 h, 24 h, 48 h and 72 h after LPS injection, the contents of TNF-α and IL-6 in bronchoalveolar lavage fluid (BALF) were detected by ELISA method. The activity of myeloperoxidase (MPO) and the content of protein in BALF were evaluated by chemical technique. The protein level of nuclear YAP, cytosol phosphorylated YAP (P-YAP), connective tissue growth factor (CTGF) and proliferating cell nuclear antigen (PCNA) in lung were analyzed by Western blot. RESULTS:The protein level of nuclear YAP at 24 h, 48 h and 72 h in lung of LPS+XMU group were up-regulated than those of LPS group by 39.2%, 148.1% and 42.9%, and the protein level of CTGF in lung were up-regulated than those of LPS group by 186.6%, 10.1% and 146.1% (P<0.05), respectively, while the protein level of cytosol P-YAP was down-regulated. The content of IL-6 and TNF-α at 24 h in BALF of LPS+XMU group were lower than those of LPS group by 28.4% and 23.7%, and the activity of MPO and the content of TNF-α at 48 h in BALF were lower by 13.5% and 39.5%, and the content of IL-6 and TNF-α at 72 h in BALF were lower by 42.8% and 16.7% (P<0.05), respectively. The protein level of PCNA at 48 h and 72 h in lung of LPS+XMU group were up-regulated than those of LPS group by 44.2% and 14.9% (P<0.05), respectively, while there was no significant difference at 24 h. The content of protein at 24 h, 48 h and 72 h in BALF of LPS+XMU group were lower than those of LPS group by 32.4%, 46.0% and 26.3% (P<0.05), respectively. The pathological changes showed a significantly attenuated tissue injury and accelerated recovery from lung injury in LPS+XMU group compared with mice injected with LPS alone at each times point. CONCLUSION: Stimulation of YAP activity attenuates lung injury and promotes lung recovery by alleviating lung inflammation and injury at injury phase, but by promoting inflammation resolution and stimulating cell proliferation at repair phase.
ABSTRACT
Objective To explore the effect of in utero exposure to inlfammation on innate immune response in preterm infants. Methods Forty-seven premature infants with gestational age<35 weeks were recruited in this study. According to his-tological evidence of placental infection, all neonates were divided into intrauterine inlfammation positive group and negative group. Mononuclear cells and monocytes were isolated from umbilical cord blood, and were cultured in vitro in the presence or absence of LPS (100 ng/ml). The levels of interleukin 1β(IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) in cord blood plasma and monocyte cultural supernatants were measured by ELISA respectively. The level of IL-1β, TNF-α, IL-6 and IL-10 mRNA were detected by Real-time PCR. Expression of HLA-DR on surface of CD14+monocytes and ratio of CD3+CD4+/CD3+CD8+T was analyzed by lfow cytometry. Results (1) The level of cord plasma IL-6 in intrauterine inlfammation positive group was signiifcantly higher than in negative group. (P=0.02). (2) After stimulation of LPS, levels of IL-1β, IL-6, TNF-α, IL-10 in supernatants were increased signiifcantly, in consistence with their mRNA expression (P<0.05) in both groups. (3) Expression of HLA-DR on surface of monocytes was signiifcantly decreased after stimulation with LPS in intrauterine inlfammation positive group (P=0.012), but was signiifcantly increased in negative group (P=0.0305). Con-clusions In utero exposure to inlfammation does not suppress the response of monocytes to LPS in preterm neonates, but impairs the antigen presenting function in monocytes.