alpha1-Antitrypsin regulates CD14 expression and soluble CD14 levels in human monocytes in vitro

The recognition of bacterial lipopolysaccharide (LPS) is principally mediated by either membrane-bound or soluble form of the glycoprotein CD14 and CD14-associated signal transducer, toll-like receptor 4 (TLR4). Recent findings indicate that the serine protease inhibitor, alpha1-antitrypsin (AAT), m...

Full description

Saved in:
Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2007, Vol.39 (6), p.1165-1176
Main Authors: Nita, Izabela M, Serapinas, Danielius, Janciauskiene, Sabina M
Format: Article
Language:English
Subjects:
alpha 1-Antitrypsin - pharmacology
Blotting, Western
Cells, Cultured
Cytokines - genetics
Cytokines - metabolism
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Gene Expression Regulation - drug effects
Humans
Interleukin-1beta - genetics
Interleukin-1beta - metabolism
Interleukin-8 - genetics
Interleukin-8 - metabolism
Lipopolysaccharide Receptors - genetics
Lipopolysaccharide Receptors - metabolism
Lipopolysaccharides - pharmacology
Monocytes - cytology
Monocytes - drug effects
Monocytes - metabolism
NF-kappa B - genetics
NF-kappa B - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Serine Proteinase Inhibitors - pharmacology
Solubility
Time Factors
Toll-Like Receptor 4 - genetics
Toll-Like Receptor 4 - metabolism
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - metabolism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The recognition of bacterial lipopolysaccharide (LPS) is principally mediated by either membrane-bound or soluble form of the glycoprotein CD14 and CD14-associated signal transducer, toll-like receptor 4 (TLR4). Recent findings indicate that the serine protease inhibitor, alpha1-antitrypsin (AAT), may not only afford protection against proteolytic injury, but may also neutralize microbial activities and affect regulation of innate immunity. We postulated that AAT affects monocyte responses to LPS by regulating CD14 expression and soluble CD14 release. Here we show that a short-term (up to 2h) monocyte exposure to AAT alone or in combination with LPS leads to a remarkable induction of CD14 levels. In parallel, a short-term (2h) cell exposure to AAT/LPS significantly enhances LPS-induced NF kappaB (p50 and p65) activation in conjunction with increased TNFalpha, IL-1 beta and IL-8 release. In contrast, longer term incubation (18 h) of monocytes with combined AAT/LPS results in a significant reduction in expression of both CD14 and TLR4, inhibition of LPS-induced TNFalpha, IL-1 beta and IL-8 mRNA and protein expression. These findings provide evidence that AAT is an important regulator of CD14 expression and release in monocytes and suggest that AAT may be involved in LPS neutralization and prevention of over-activation of monocytes in vivo.
ISSN:1357-2725
1878-5875