alpha(1)-Antitrypsin, old dog, new tricks - alpha 1-Antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevatin cAMP
(2007) In Journal of Biological Chemistry 282(12). p.8573-8582- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/665973
- author
- Janciauskiene, Sabina LU ; Nita, Izabela LU and Stevens, Tim
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 282
- issue
- 12
- pages
- 8573 - 8582
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000245780300003
- scopus:34247884585
- pmid:17261591
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M607976200
- language
- English
- LU publication?
- yes
- id
- 84cb0dcf-9ed4-4338-b471-780477194ba6 (old id 665973)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17261591&dopt=Abstract
- date added to LUP
- 2016-04-01 12:00:03
- date last changed
- 2022-04-21 00:58:09
@article{84cb0dcf-9ed4-4338-b471-780477194ba6, 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.}}, author = {{Janciauskiene, Sabina and Nita, Izabela and Stevens, Tim}}, issn = {{1083-351X}}, language = {{eng}}, number = {{12}}, pages = {{8573--8582}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Biological Chemistry}}, title = {{alpha(1)-Antitrypsin, old dog, new tricks - alpha 1-Antitrypsin exerts in vitro anti-inflammatory activity in human monocytes by elevatin cAMP}}, url = {{https://lup.lub.lu.se/search/files/8169101/625884.pdf}}, doi = {{10.1074/jbc.M607976200}}, volume = {{282}}, year = {{2007}}, }