Concentration-dependent effects of native and polymerised alpha 1-antitrypsin on primary human monocytes, in vitro

Ruta Aldonyte, Lennart Jansson, Sabina Janciauskiene

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

41 Citeringar (SciVal)

Sammanfattning

Background: alpha1-antitrypsin (AAT) is one of the major serine proteinase inhibitors controlling proteinases in many biological pathways. There is increasing evidence that AAT is able to exert other than antiproteolytic effects. To further examine this question we compared how various doses of the native (inhibitory) and the polymerised (non- inhibitory) molecular form of AAT affect pro-inflammatory responses in human monocytes, in vitro. Human monocytes isolated from different donors were exposed to the native or polymerised form of AAT at concentrations of 0.01, 0.02, 0.05, 0.1, 0.5 and 1 mg/ml for 18 h, and analysed to determine the release of cytokines and to detect the activity of NF-kappaB. Results: We found that native and polymerised AAT at lower concentrations, such as 0.1 mg/ml, enhance expression of TNFalpha (10.9- and 4.8-fold, p < 0.001), IL-6 (22.8- and 23.4-fold, p < 0.001), IL-8 (2.4- and 5.5-fold, p < 0.001) and MCP-1 (8.3- and 7.7-fold, p < 0.001), respectively, compared to buffer exposed cells or cells treated with higher doses of AAT ( 0.5 and 1 mg/ml). In parallel to increased cytokine levels, low concentrations of either conformation of AAT (0.02-0.1 mg/ml) induced NF-kappaB p50 activation, while 1 mg/ml of either conformation of AAT suppressed the activity of NF-kappaB, compared to controls. Conclusions: The observations reported here provide further support for a central role of AAT in inflammation, both as a regulator of proteinase activity, and as a signalling molecule for the expression of pro-inflammatory molecules. This latter role is dependent on the concentration of AAT, rather than on its proteinase inhibitory activity.
Originalspråkengelska
TidskriftBMC Cell Biology
Volym5
DOI
StatusPublished - 2004

Bibliografisk information

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Chronic Inflammatory and Degenerative Diseases Research Unit (013242530), Preventive Paediatrics (013243030)

Ämnesklassifikation (UKÄ)

  • Klinisk medicin
  • Pediatrik
  • Reumatologi och inflammation

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