title: Surfactant blocks lipopolysaccharide signaling by inhibiting both NFκB and PARP activation in experimental ARDS.
abstract: Surfactant plays an important role in lung homeostasis and is also involved in maintaining innate immunity within the lung. Lipopolysaccharide (LPS) is known to elicit acute proinflammatory responses in lung diseases such as acute respiratory distress syndrome and is responsible for the expression of the inducible isoform of nitric oxide synthase (iNOS). Because cells are exposed to low pH within the microenvironment of inflammatory lesions, the potential role of low environmental pH on iNOS expression was investigated. Low environmental pH-induced iNOS gene transcription involved the activation of nuclear factor-κB (NF-κB) transcription factor and IκB kinases. Here, we find that exposure of cells to low environmental pH increased both nitrite accumulation and activation of NF-κB-signaling pathway by Western blot and immunohistochemistry. In addition, treatment with surfactant prevents NF-κB translocation to the nucleus by preventing phosphorylation of IκBα, and its subsequent degradation by IKKα, and canceling low pH-induced nitrite accumulation. Surfactant also inhibited the LPS-induced PARP activation. Therefore, surfactant may regulate lung homeostasis by neutralizing acidic microenvironment in inflammatory lesions that leads to the upregulation of iNOS activity through the activation of NF-κB pathway and by PARP activation.
authors: Department of Biophysics, Panjab University, Chandigarh 160014, India.
authors: Neha
authors: N
authors: Mittal
authors: Sankar Nath
authors: SN
authors: Sanyal
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology / Q000627:therapeutic use; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002956:Citrulline / Q000378:metabolism; D004338:Drug Combinations; D004789:Enzyme Activation; D005233:Fatty Alcohols / Q000494:pharmacology / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D051550:I-kappa B Kinase / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D013552:Swine
chemical_list: D004338:Drug Combinations; D005233:Fatty Alcohols; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011663:Pulmonary Surfactants; C082161:lipopolysaccharide A; D015060:1,2-Dipalmitoylphosphatidylcholine; D002956:Citrulline; D011092:Polyethylene Glycols; C005031:cetyl alcohol; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D051550:I-kappa B Kinase; C016811:tyloxapol