Fas/FADD-mediated activation of a specific program of inflammatory gene expression in vascular smooth muscle cells.
Apoptosis of smooth muscle cells is a common feature of vascular lesions but its pathophysiological significance is not known. We demonstrate that signals initiated by regulated Fas-associated death domain protein overexpression in rat vascular smooth muscle cells in the carotid artery induce expression of monocyte-chemoattractant protein-1 and interleukin-8, and cause massive immigration of macrophages in vivo. These chemokines, and a specific set of other pro-inflammatory genes, are also upregulated in human vascular smooth muscle cells during Fas-induced apoptosis, in part through a process that requires interleukin-1alpha activation. Induction of a pro-inflammatory program by apoptotic vascular smooth muscle cells may thus contribute to the pathogenesis of vascular disease.
Schaub
F J
FJ
Department of Pathology, Box 357470, University of Washington, Washington 98195-7470, USA.
Han
D K
DK
Liles
W C
WC
Adams
L D
LD
Coats
S A
SA
Ramachandran
R K
RK
Seifert
R A
RA
Schwartz
S M
SM
Bowen-Pope
D F
DF
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis; D053200:Fas-Associated Death Domain Protein; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis; D009131:Muscle, Smooth, Vascular / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation; D019014:fas Receptor / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018932:Chemokine CCL2; C505533:FADD protein, human; C505535:Fadd protein, rat; D053200:Fas-Associated Death Domain Protein; D007375:Interleukin-1; D016209:Interleukin-8; D019014:fas Receptor; D020169:Caspases