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Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an effect on the ubiquitin-proteasome pathway.

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posted on 22.11.2019 by Marcus W. Butler, Ian Robertson, Catherine M. Greene, Shane J. O'Neill, Clifford C. Taggart, Noel G. McElvaney
The serine anti-protease elafin is expressed by monocytes, alveolar macrophages, neutrophils, and at mucosal surfaces and possesses antimicrobial activity. It is also known to reduce lipopolysaccharide-induced neutrophil influx into murine alveoli as well as to abrogate lipopolysaccharide-induced production of matrix metalloprotease 9, macrophage inhibitory protein 2, and tumor necrosis factor-alpha by as-yet unidentified mechanisms. In this report we have shown that elafin inhibits the lipopolysaccharide-induced production of monocyte chemoattractant protein-1 in monocytes by inhibiting AP-1 and NF-kappaB activation. Elafin prevented lipopolysaccharide-induced phosphorylation of AP-1, c-Jun, and JNK but had no effect on phosphorylation of p38. The lipopolysaccharide-induced degradation of IL-1R-associated kinase 1, IkappaBalpha, and IkappaBbeta was inhibited by elafin but phosphorylation of IkappaBalpha was unaffected. Polyubiquitinated protein including polyubiquitinated IkappaBalpha was shown to accumulate in the presence of elafin. These results suggest that inhibition by elafin of lipopolysaccharide-induced AP-1 and NF-kappaB activation occurs via an effect on the ubiquitin-proteasome pathway.

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Available in the Journal of Biological Chemistry at http://www.jbc.org/

Published Citation

Butler M W,Robertson I, Greene CM, Shane J O'Neill SJ, Taggart CC, McElvaney NG. Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an effect on the ubiquitin-proteasome pathway. Journal of Biological Chemistry 2006; 281(46):34730-5.

Publication Date

17/11/2006

Publisher

American Society for Biochemistry and Molecular Biology

PubMed ID

16980310

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