| Autor: |
Martin-Manso, Gema, Mosher, Deane F., Roberts, David D. |
| Předmět: |
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| Zdroj: |
FASEB Journal; Apr2007, Vol. 21 Issue 6, pA1146-A1146, 1/4p |
| Abstrakt: |
Thrombospondin-1 (TSP1) is a glycoprotein secreted by many cell types that modulates cell adhesion, growth, motility, differentiation, and survival. We investigated regulatory effects of TSP1 on phorbol ester (PMA)-mediated superoxide generation from human U937 monocytic cells differentiated with recombinant human interferon-gamma. Soluble TSP1 caused a significant increase in PMA-mediated superoxide generation. Trimeric recombinant constructs containing the N-modules, but not other recombinant regions of TSP1, replicated the activity of TSP1. A similar effect of TSP1 on superoxide generation has been described in human neutrophils. The superoxide-generated via NADPH oxidase is an important component of the innate immune response. An important target of NADPH oxidase-derived radicals is the ubiquitous transcription factor NF-kappaB, which controls the expression of many genes involved in immune function and cell survival. Here we show that soluble TSP1 causes a significant increase in PMA-mediated NF-kappaB activation in human macrophages. Together, the present findings indicate that TSP1 enhances PMA-mediated superoxide generation from human macrophages through its N-terminal region, suggesting a physiological function of TSP1 in regulation of innate immune responses. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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