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

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alpha1-Antitrypsin regulates CD14 expression and soluble CD14 levels in human monocytes in vitro. / Nita, Izabela; Serapinas, Danielius; Janciauskiene, Sabina.

In: International Journal of Biochemistry & Cell Biology, Vol. 39, No. Mar 1, 2007, p. 1165-1176.

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T1 - alpha1-Antitrypsin regulates CD14 expression and soluble CD14 levels in human monocytes in vitro.

AU - Nita, Izabela

AU - Serapinas, Danielius

AU - Janciauskiene, Sabina

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - TLR4

KW - CD14

KW - lipopolysaccharide

KW - alpha 1-antitrypsin

KW - monocytes

KW - inflammation

KW - cytokines

U2 - 10.1016/j.biocel.2007.02.017

DO - 10.1016/j.biocel.2007.02.017

M3 - Article

VL - 39

SP - 1165

EP - 1176

JO - International Journal of Biochemistry and Cell Biology

JF - International Journal of Biochemistry and Cell Biology

SN - 1878-5875

IS - Mar 1

ER -