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

Nita, Izabela LU ; Serapinas, Danielius and Janciauskiene, Sabina LU (2007) In International Journal of Biochemistry & Cell Biology 39(Mar 1). p.1165-1176
Abstract
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, alpha 1-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 CD 14 release. Here we show that a short-term (up to 2 h) monocyte exposure to AAT alone or in combination with LPS leads to a remarkable induction of CD 14 levels. In parallel, a short-term (2 h) cell... (More)
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, alpha 1-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 CD 14 release. Here we show that a short-term (up to 2 h) monocyte exposure to AAT alone or in combination with LPS leads to a remarkable induction of CD 14 levels. In parallel, a short-term (2 h) cell exposure to AAT/LPS significantly enhances LPS-induced NF kappa B (p50 and p65) activation in conjunction with increased TNF alpha, IL-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 CD 14 and TLR4, inhibition of LPS-induced TNF alpha, IL-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. (C) 2007 Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
TLR4, CD14, lipopolysaccharide, alpha 1-antitrypsin, monocytes, inflammation, cytokines
in
International Journal of Biochemistry & Cell Biology
volume
39
issue
Mar 1
pages
1165 - 1176
publisher
Elsevier
external identifiers
  • wos:000247548000011
  • scopus:34249332725
ISSN
1878-5875
DOI
10.1016/j.biocel.2007.02.017
language
English
LU publication?
yes
id
88e7e0e6-4e75-4286-b1ac-94810b5213b8 (old id 167487)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17448722&dopt=Abstract
date added to LUP
2007-07-27 10:58:39
date last changed
2017-01-01 06:40:46
@article{88e7e0e6-4e75-4286-b1ac-94810b5213b8,
  abstract     = {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, alpha 1-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 CD 14 release. Here we show that a short-term (up to 2 h) monocyte exposure to AAT alone or in combination with LPS leads to a remarkable induction of CD 14 levels. In parallel, a short-term (2 h) cell exposure to AAT/LPS significantly enhances LPS-induced NF kappa B (p50 and p65) activation in conjunction with increased TNF alpha, IL-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 CD 14 and TLR4, inhibition of LPS-induced TNF alpha, IL-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. (C) 2007 Elsevier Ltd. All rights reserved.},
  author       = {Nita, Izabela and Serapinas, Danielius and Janciauskiene, Sabina},
  issn         = {1878-5875},
  keyword      = {TLR4,CD14,lipopolysaccharide,alpha 1-antitrypsin,monocytes,inflammation,cytokines},
  language     = {eng},
  number       = {Mar 1},
  pages        = {1165--1176},
  publisher    = {Elsevier},
  series       = {International Journal of Biochemistry & Cell Biology},
  title        = {alpha1-Antitrypsin regulates CD14 expression and soluble CD14 levels in human monocytes in vitro.},
  url          = {http://dx.doi.org/10.1016/j.biocel.2007.02.017},
  volume       = {39},
  year         = {2007},
}