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

Sabina Janciauskiene, Izabela Nita, Tim Stevens

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    116 Citations (SciVal)
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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.
    Original languageEnglish
    Pages (from-to)8573-8582
    JournalJournal of Biological Chemistry
    Volume282
    Issue number12
    DOIs
    Publication statusPublished - 2007

    Subject classification (UKÄ)

    • Rheumatology and Autoimmunity

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