Tenascin-C Produced by Oxidized LDL-Stimulated Macrophages Increases Foam Cell Formation through Toll-like Receptor-4

다국어 초록 (Multilingual Abstract)

Atherosclerosis is a chronic inflammatory disease in which both innate and adaptive immunity are involved. Although there have been major advances in the involve-ment 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 TN-C produced by oxLDL-stimulated macrophages increases foam cell formation through TLR4 and scavenger receptor CD36.

참고문헌 (Reference)

1 Ricciarelli, R., "Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger receptor expression in cultured aortic smooth muscle cells" 102 : 82-87, 2000

2 Takeda, K., "Toll-like receptors" 21 : 335-376, 2003

3 Xu, X. H., "Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL" 104 : 3103-3108, 2001

4 Howell, K. W., "Toll-like receptor 4 mediates oxidized LDL-induced macrophage differentiation to foam cells" 171 : 27-31, 2011

5 Libby, P., "The immune response in atherosclerosis: a doubleedged sword" 6 : 508-519, 2006

6 Chiquet-Ehrismann, R., "Tenascins: regulation and putative functions during pathological stress" 200 : 488-499, 2003

7 Kim, M., "Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease" 15 : 774-781, 2009

8 Midwood, K., "Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease" 15 : 774-780, 2009

9 Jiang, L., "Synergistic effects of cyclic strain and Th1-like cytokines on tenascin-C production by rheumatic aortic valve interstitial cells" 155 : 216-223, 2009

10 Ashraf, M. Z., "Scavenger receptors: implications in atherothrombotic disorders" 43 : 697-700, 2011

11 Watanabe, T., "Role of macrophages in atherosclerosis. Sequential observations of cholesterol-induced rabbit aortic lesion by the immunoperoxidase technique using monoclonal antimacrophage antibody" 53 : 80-, 1985

12 Stuart, L. M., "Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain" 170 : 477-485, 2005

13 Ito, T., "Progression of coronary atherosclerosis relates to the onset of myocardial infarction in an animal model of spontaneous myocardial infarction (WHHLMI rabbits)" 53 : 339-346, 2004

14 Podrez, E. A., "Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype" 13 : 1086-1095, 2007

15 Khan, Z. A., "Oncofetal fibronectin in diabetic retinopathy" 45 : 287-, 2004

16 Tedgui, A., "Nobel prize in physiology or medicine" 31 : 2767-2768, 2011

17 Han, J., "Native and modified low density lipoproteins increase the functional expression of the macrophage class B scavenger receptor, CD36" 272 : 21654-, 1997

18 Hajjar, D. P., "Lipoprotein trafficking in vascular cells" 272 : 22975-, 1997

19 Feng, X., "Lipopolysaccharide up-regulates the expression of Fc [alpha]/[mu] receptor and promotes the binding of oxidized low-density lipoprotein and its IgM antibody complex to activated human macrophages" 208 : 396-405, 2010

20 Hansson, G. K., "Inflammation, atherosclerosis, and coronary artery disease" 352 : 1685-1695, 2005

21 Amin, K., "Inflammation and structural changes in the airways of patients with primary Sjögren’s syndrome" 95 : 904-910, 2001

22 Ishigaki, Y., "Impact of plasma oxidized low-density lipoprotein removal on atherosclerosis" 118 : 75-83, 2008

23 Jovinge, S., "Human monocytes/macrophages release TNF-α in response to ox-LDL. Arterioscler" 16 : 1573-1579, 1996

24 Chang, Y. C., "Hibiscus anthocyanins-rich extract inhibited LDL oxidationand oxLDL-mediated macrophages apoptosis" 44 : 1015-1023, 2006

25 Udalova, I. A., "Expression and immune function of tenascin-C" 31 : 115-145, 2011

26 Loots, M. A. M., "Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds" 111 : 850-857, 1998

27 Stewart, C. R., "CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer" 11 : 155-161, 2009

28 Hoebe, K., "CD36 is a sensor of diacylglycerides" 433 : 523-527, 2005

29 Munteanu, A., "Antagonistic effects of oxidized low density lipoprotein and α-Tocopherol on CD36 scavenger receptor expression in monocytes" 281 : 6489-6497, 2006

30 Midwood, K. S., "Advances in tenascin-C biology" 68 : 3175-3199, 2011

31 Lahoute, C., "Adaptive immunity in atherosclerosis: mechanisms and future therapeutic targets" 8 : 348-358, 2011

32 Andersson, J., "Adaptive immunity and atherosclerosis" 134 : 33-46, 2010