| Surfactant blocks lipopolysaccharide signaling by inhibiting both NFκB and PARP activation in experimental ARDS. | |
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MedLine Citation:
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PMID: 21461608 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Neha Mittal; Sankar Nath Sanyal |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-2 |
Journal Detail:
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Title: Molecular and cellular biochemistry Volume: - ISSN: 1573-4919 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Biophysics, Panjab University, Chandigarh, 160014, India. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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