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Structure and functions of tumor necrosis factor-alpha converting enzyme

100%

Mezyk R. , Bzowska M. , Bereta J.

tom 50

nr 3

Tumor necrosis factor-a converting enzyme (TACE) is the first described and best characterized secretase. In this review the structure and the possible roles for TACE are summarized. The substrate specificity and the regulation of TACE activity as well as redundancy and possible cooperations of distinct secretases are also discussed.

Exogenous nitric oxide inhibits shedding of ADAM17 substrates

76%

Bzowska M. , Stalinska K. , Mezyk-Kopec R. , Wawro K. , Duda K. , Das S. , Bereta J.

nr 2

325-335

Both ADAM17, the secretase responsible for the shedding of ectodomains of numerous membrane proteins including TNF and its receptors, as well as nitric oxide synthesized by inducible nitric oxide synthase play regulatory roles in inflammation and tumor progression. We analyzed the effect of endogenous and exogenous nitric oxide on the expression and activity of ADAM17 in murine endothelial cells and a monocyte/macrophage cell line. We found that endogenous nitric oxide influenced neither ADAM17 mRNA level nor the shedding of two ADAM17 substrates, TNF and TNFR1. Exogenous NO significantly diminished the release of TNF and TNFR1 without affecting the ADAM17 transcript level. Our data seem contrary to a previous report that showed the activation of ADAM17 by nitric oxide (Zhang et al., 2000, J Biol Chem 275: 15839-15844). We discuss potential mechanisms of NO-mediated inhibition of ectodomain shedding and possible reasons of discrepancy between our results and the previous report.

Modulation of acute phase protein synthesis by cellular growth and differentiation factors

75%

Koj A. , Rokita H. , Pierzchalski P. , Kordula T. , Guzdek A. , Bereta J.

nr 4

Anti-inflammatory effects of extracts from some traditional Mediterranean diet plants

63%

Strzelecka M. , Bzowska M. , Koziel J. , Szuba B. , Dubiel O. , Rivera Nunez D. , Heinrich M. , Bereta J.

nr 1

139-156

It is believed that bioactive compounds from plant foods may have health beneficial effects and reduce the risk of chronic inflammatory diseases. In this study extracts of 121 plants typical for the traditional Mediterranean diet have been screened for their potential anti-inflammatory activities. The ability of the extracts to inhibit cytokinestimulated, iNOS-dependent synthesis of nitric oxide in murine endothelial cells, without affecting cell viability, was the primary indicator of their anti-inflammatory properties. Based on these experiments we selected eight plant extracts for further analysis: Chrysanthemum coronarium L., Scandix pecten-veneris L., Urospermum picroides (L.) Scop. Ex F. W. Smith, Amaranthus cf. graecizans L., Onopordum macracanthum Schousboe, Eryngium campestre L., Artemisia alba Turra and Merendera pyrenaica (Pourret) Fourn. Only the effects of Onopordum macracanthum could be non-specific since the extract strongly inhibited total protein synthesis. All remaining 7 extracts decreased nitric oxide and TNFa synthesis in the cells of monocyte origin activated with LPS, and 4 of them significantly reduced surface expression of VCAM1 on TNFa-stimulated endothelial cells. All seven plant extracts decreased cytokine or LPS-stimulated iNOS mRNA levels in both cell types. Further research to identify bioactive compounds influencing intracellular signaling pathways activated by cytokines and LPS will consequently be needed in order to better understand these in vitro effects.