[The two sides of ADAM17 in inflammation: implications in atherosclerosis and obesity].
ADAM17 was initially characterized as the TNF Alpha Converting Enzyme (TACE) and, until now, has been the most studied member of the ADAM family. It is a type I transmembrane metalloproteinase involved in the shedding of the extracellular domain of several transmembrane proteins (at least 40) such as cytokines, growth factors, receptors or adhesion molecules. As a consequence, depending on the transmembrane molecule cleaved, one may expect possible opposite effects of ADAM17 activity on inflammation (e.g. TNF and its receptors). The role of ADAM17 in regulating inflammatory cellular processes is clearly demonstrated in cells deficient in active ADAM17 or expressing substrates mutated for the ADAM17 cleavage site. As ADAM17-deficient mice died at birth, mice overexpressing the mutated uncleavable form of some substrates and recently conditional knock-out of ADAM17 are used to approach in vivo the role of this metalloprotease in regulating inflammation. Arguments are provided that ADAM17 plays a role in atherosclerosis, in adipose tissue metabolism, insulin resistance and diabetes. The multitude of substrates cleaved by ADAM17 makes this enzyme an attractive candidate to study its role in inflammation-driven pathologies.
Peiretti
Franck
F
Inserm U626, Faculté de Médecine, 27, boulevard Jean Moulin, 13385 Marseille Cedex 5, France. franck.peiretti@univmed.fr
Canault
Matthias
M
Morange
Pierre
P
Alessi
Marie-Christine
MC
Nalbone
Gilles
G
D051722:ADAM Proteins / Q000172:deficiency / Q000502:physiology*; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000502:physiology; D000818:Animals; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000201:enzymology / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D009765:Obesity / Q000201:enzymology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D014409:Tumor Necrosis Factor-alpha; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606463:Adam17 protein, mouse