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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Reumatologi och inflammation
Originalspråkengelska
Sidor (från-till)8573-8582
TidskriftJournal of Biological Chemistry
Volym282
Utgivningsnummer12
StatusPublished - 2007
PublikationskategoriForskning
Peer review utfördJa

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Relaterad forskningsoutput

Nita, I., 2009, Institutionen för kliniska vetenskaper, Lunds universitet. 167 s.

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

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