Accumulation of inhibitory κB-α as a mechanism contributing to the anti-inflammatory effects of surfactant protein-A

Yingda Wu, Stefanie Adam, Lutz Hamann, Holger Heine, Artur J. Ulmer, Ute Buwitt-Beckmann, Cordula Stamme*

*Korrespondierende/r Autor/-in für diese Arbeit
33 Zitate (Scopus)

Abstract

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 KB (IκB)/nuclear factor (NF)-κB 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-κB-dependent CD25 expression in these cells. In AMs, SP-A pretreatment caused a marked inhibition of lipopolysaccharide (LPS)-induced NF-κB 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 IκB-α, the predominant regulator for rapidly induced NF-κB, in a dose- and time-dependent manner without enhancing IκB-α messenger RNA as determined by reverse transcription-polymerase chain reaction. SP-A did not interfere with LPS-induced serine32 phosphorylation of IκB-α but significantly enhanced IκB-α abundance under LPS-coupled conditions. The data suggest that anti-inflammatory effects of SP-A on LPS-challenged AMs are associ ated with a SP-A-mediated direct modulation of the IκB-α turnover in these cells.

OriginalspracheEnglisch
ZeitschriftAmerican Journal of Respiratory Cell and Molecular Biology
Jahrgang31
Ausgabenummer6
Seiten (von - bis)587-594
Seitenumfang8
ISSN1044-1549
DOIs
PublikationsstatusVeröffentlicht - 12.2004

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