alpha(1)-Antitrypsin, old dog, new tricks - alpha 1-Antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevatin cAMP

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Abstract

Regulation of serine protease activity is considered to be the sole mechanism for the function of alpha(1)-antitrypsin (AAT). However, recent reports of the anti-inflammatory effects of AAT are hard to reconcile with this classical mechanism. We discovered that two key activities of AAT in vitro, namely inhibition of endotoxin-stimulated tumor necrosis factor-a and enhancement of interleukin-10 in human monocytes, are mediated by an elevation of cAMP and activation of cAMP-dependent protein kinase A. As expected with this type of mechanism, the AAT mediated rise in cAMP and the impact on endotoxin-stimulated tumor necrosis factor-a and interleukin-10 was enhanced when the catabolism of cAMP was blocked by the phosphodiesterase inhibitor rolipram. These effects were still observed with modified forms of AAT lacking protease inhibitor activity.

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Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity
Original languageEnglish
Pages (from-to)8573-8582
JournalJournal of Biological Chemistry
Volume282
Issue number12
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes

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