Abstract
Background LBP and fractalkine are known to be involved in the pathogenesis of ARDS. This study investigated the relationship between LBP and fractalkine in LPS-induced A549 cells and rat lung tissue in an ARDS rat model. Methods A549 cells were transfected with LBP or LBP shRNA plasmid DNA or pretreated with SB203580 or SC-514 following LPS treatment. An ARDS rat model was established using LPS with or without LBPK95A, SB203580, or SC-514 treatment. RT-PCR, western blotting, ELISA, immunofluorescence, coimmunoprecipitation, and immunohistochemical staining were used to study the expression of fractalkine and LBP and p38 MAPK and p65 NF-κB activities. Results LPS increased LBP and reduced fractalkine. LBP overexpression further decreased LPS-induced downregulation of fractalkine and p38 MAPK and p65 NF-κB activation; LBP gene silencing, SB203580, and SC-514 suppressed LPS-induced downregulation of fractalkine and p38 MAPK and p65 NF-κB activation in A549 cells. LBP and fractalkine in lung tissue were increased and decreased, respectively, following LPS injection. LBPK95A, SB203580, and SC-514 ameliorated LPS-induced rat lung injury and suppressed LPS-induced downregulation of fractalkine by decreasing phospho-p38 MAPK and p65 NF-κB. Conclusions The results indicate that LBP downregulates fractalkine expression in LPS-induced A549 cells and in an ARDS rat model through activation of p38 MAPK and NF-κB.
Highlights
Acute respiratory distress syndrome (ARDS) is associated with high mortality and morbidity [1, 2]
The results suggested that LPS induced the activation of phospho-p38 mitogen-activated protein kinase (MAPK) and phospho-p65 in the ARDS rat model
We showed that LPS increased the Lipopolysaccharide-binding protein (LBP) mRNA and protein expression in A549 cells and the LPS-induced ARDS rats
Summary
Acute respiratory distress syndrome (ARDS) is associated with high mortality and morbidity [1, 2]. ARDS is characterized by neutrophilic inflammation, pulmonary edema, hemorrhage, alveolar-capillary destruction, and hyaline membrane formation in the lung resulting subsequently in alveolar flooding and acute respiratory failure [3, 4]. This study investigated the relationship between LBP and fractalkine in LPS-induced A549 cells and rat lung tissue in an ARDS rat model. An ARDS rat model was established using LPS with or without LBPK95A, SB203580, or SC-514 treatment. LBP and fractalkine in lung tissue were increased and decreased, respectively, following LPS injection. LBPK95A, SB203580, and SC-514 ameliorated LPS-induced rat lung injury and suppressed LPS-induced downregulation of fractalkine by decreasing phospho-p38 MAPK and p65 NF-κB. The results indicate that LBP downregulates fractalkine expression in LPS-induced A549 cells and in an ARDS rat model through activation of p38 MAPK and NF-κB
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