Abstract
Background Abundant reports have uncovered an imbalance of Treg and Th17 cells in pulmonary diseases. Hereon, we intend to explore the impact of PARP-1 on the imbalance of Th17/Treg and the potential mechanism in premature rats with acute respiratory distress syndrome (ARDS). Methods Preterm ARDS infants and healthy term infants were enrolled in this investigation. To induce a rat model of ARDS, E.coli suspension was given to rats through two vaginal dilator-guided intramuscular injections. H&E staining was used to perform histopathological examination. Flow cytometry was employed to assess the proportion of Th17 or Treg cells accounted for CD4+ T cells. ELISA was applied to measure levels of IL-6, IL-17A, and IL-10 in the serum of ARDS patients. Moreover, the mRNA and protein expression levels of PARP-1, IL-6, IL-17A, and IL-10 were detected through qRT-PCR and western blotting. Results An increased Th17/Treg ratio was observed in preterm infants and rats with ARDS. The PARP-1 expression level was raised in the lung tissues of ARDS rats, and PARP-1 downregulation alleviated E.coli-induced lung injury in preterm rats. Expression levels of PARP-1, IL-6, and IL-17A were raised, and the IL-10 level was reduced in the lung tissues of rats after E.coli treatment, which was all reversed by PARP-1 suppression. Importantly, the ratio of Th17/Treg differentiated from purified CD4+ T cells of the E.coli + PARP-1 inhibitor group was elevated by recombinant IL-6. Conclusion PARP-1 downregulation repressed the imbalance of Th17 and Treg cells via reducing the expression level of IL-6, implying that PARP-1 may be a promising target for ARDS therapy.
Highlights
Acute respiratory distress syndrome (ARDS) is acknowledged to be a serious form of lung injury [1]
17/Treg secretory cytokines were measured via Enzyme-Linked Immunosorbent Assay (ELISA), which showed that serum levels of IL-17A (P < 0.001) in cells and IL-10 (P < 0.05) in Treg cells were all boosted in acute respiratory distress syndrome (ARDS) infants compared to healthy controls (P < 0.001; Figure 1(c))
It turned out that mRNA and protein levels of PARP-1, IL-6, and IL-17A in the lung tissues of rats were raised and the IL-10 level was reduced in response to E.coli treatment (P < 0.01), which was partially reversed by PARP-1 suppression in the lung tissues of E.coli-induced pregnant rats (E18) and neonatal rats (P1) (P < 0.05; Figures 2(d) and 2(e)). erefore, we inferred that PARP-1 downregulation alleviated lung injury in E.coli-induced rats
Summary
Abundant reports have uncovered an imbalance of Treg and 17 cells in pulmonary diseases. We intend to explore the impact of PARP-1 on the imbalance of 17/Treg and the potential mechanism in premature rats with acute respiratory distress syndrome (ARDS). An increased 17/Treg ratio was observed in preterm infants and rats with ARDS. E PARP-1 expression level was raised in the lung tissues of ARDS rats, and PARP-1 downregulation alleviated E.coli-induced lung injury in preterm rats. Expression levels of PARP-1, IL-6, and IL-17A were raised, and the IL-10 level was reduced in the lung tissues of rats after E.coli treatment, which was all reversed by PARP-1 suppression. The ratio of 17/Treg differentiated from purified CD4+ T cells of the E.coli + PARP-1 inhibitor group was elevated by recombinant IL-6. PARP-1 downregulation repressed the imbalance of 17 and Treg cells via reducing the expression level of IL-6, implying that PARP-1 may be a promising target for ARDS therapy
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