Tenascin-C produced by oxidized LDL-stimulated macrophages increases foam cell formation through Toll-like receptor-4.
Atherosclerosis is a chronic inflammatory disease in which both innate and adaptive immunity are involved. Although there have been major advances in the involvement of toll-like receptor 4 (TLR4) and CD36 in the initiation and development of this disease, detailed mechanisms remain unknown. Here, we show that tenascin-C (TN-C) can stimulate foam cell formation and this can be inhibited by a TLR4-blocking antibody or CD36 gene silencing. Our results identify TN-C-TLR4 activation as a common molecular mechanism in oxLDL-stimulated foam cell formation and atherosclerosis. In addition, CD36 is the major scavenger receptor responsible for the TN-C-mediated foam cell formation. Taken together, we have identified that TNC produced by oxLDL-stimulated macrophages increases foam cell formation through TLR4 and scavenger receptor CD36.
Department of Geriatrics, Tangdu hospital, The Fourth Military Medical University, Xi'an, P.R. China. speciallr@163.com
Rui
R
Liu
Yong
Y
He
Bo
B
Li
Jun
J
Liu
Yingang
Y
Ren
Wei
W
Han
Xing
X
Wang
Lihua
L
Zhang
D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005487:Foam Cells / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference; D019063:Tenascin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; C495345:TLR4 protein, human; D019063:Tenascin; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein