Accumulation of Inhibitory κB-α as a Mechanism Contributing to the Anti-Inflammatory Effects of Surfactant Protein–A
| Autor: | Yingda Wu, Ute Buwitt-Beckmann, Artur J. Ulmer, Lutz Hamann, Stefanie Adam, Holger Heine, Cordula Stamme |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
Male Pulmonary and Respiratory Medicine Lipopolysaccharide CD14 Clinical Biochemistry Anti-Inflammatory Agents Lipopolysaccharide Receptors Collectin Receptors Cell Surface CHO Cells Biology Rats Sprague-Dawley Phosphoserine chemistry.chemical_compound NF-KappaB Inhibitor alpha Western blot Cricetinae medicine Animals Electrophoretic mobility shift assay RNA Messenger Phosphorylation Molecular Biology Cells Cultured Inflammation Membrane Glycoproteins Pulmonary Surfactant-Associated Protein A medicine.diagnostic_test Macrophages Chinese hamster ovary cell Toll-Like Receptors NF-kappa B Cell Biology Molecular biology Rats Surfactant protein A Toll-Like Receptor 4 chemistry I-kappa B Proteins Signal transduction |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 31:587-594 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | The collectin surfactant protein (SP)-A has been implicated in multiple immunoregulatory functions of innate pulmonary host defense via modulating immune responses both in vitro and in vivo. The aim of the present study was to investigate mechanisms responsible for the anti-inflammatory effects of human (hu) SP-A on the inhibitory kappaB (IkappaB)/nuclear factor (NF)-kappaB signaling pathway in alveolar macrophages (AMs). Initial CD25 expression analysis by flow cytometry of CD14/hu Toll-like receptor 4-transfected Chinese hamster ovary reporter cells demonstrated that SP-A alone does not induce any NF-kappaB-dependent CD25 expression in these cells. In AMs, SP-A pretreatment caused a marked inhibition of lipopolysaccharide (LPS)-induced NF-kappaB activation independent of the LPS chemotype used as determined by electrophoretic mobility shift assay. Western blot analysis revealed that SP-A by itself increased the protein expression of IkappaB-alpha, the predominant regulator for rapidly induced NF-kappaB, in a dose- and time-dependent manner without enhancing IkappaB-alpha messenger RNA as determined by reverse transcription-polymerase chain reaction. SP-A did not interfere with LPS-induced serine(32) phosphorylation of IkappaB-alpha but significantly enhanced IkappaB-alpha abundance under LPS-coupled conditions. The data suggest that anti-inflammatory effects of SP-A on LPS-challenged AMs are associated with a SP-A-mediated direct modulation of the IkappaB-alpha turnover in these cells. |
| Databáze: | OpenAIRE |
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