CD47 Binding on Vascular Endothelial Cells Inhibits IL-17-Mediated Leukocyte Adhesion.
CD47 Binding on Vascular Endothelial Cells Inhibits IL-17-Mediated Leukocyte Adhesion.
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DOI:
10.3390/ijms23105705
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发表时间:
2022-05-20
影响因子:
5.6
通讯作者:
中科院分区:
文献类型:
--
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To address the conflicting role of thrombospondin (TSP)-1 reported in acute and chronic pathologies, this study investigated the role of TSP-1 in regulating leukocyte recruitment and regulation of VCAM-1 expression using mouse models of uveitis. The spontaneously increased VCAM-1 expression and leukocyte adhesion in retinas of TSP-1-deficient mice suggested a TSP-1-mediated regulation of VCAM-1 expression. In a chronic uveitis model, induced by immunizing wild-type mice with specific interphotoreceptor retinoid-binding protein (IRBP) peptide, topically applied TSP-1-derived CD47-binding peptide significantly reduced the clinical disease course and retinal leukocyte adhesion as compared to the control peptide-treated group. In contrast, in LPS-mediated acute uveitis, TSP-1 deficiency significantly reduced the retinal leukocyte adhesion. The results of our in vitro study, using vascular endothelial cell (EC) cultures, demonstrate that unlike TNF-α, VCAM-1 expression induced by IL-17 is associated with a reduced expression of endogenous TSP-1. Such reduced endogenous TSP-1 expression in IL-17-stimulated ECs helps limit the CD36-mediated increased VCAM-1 expression, while favoring CD47-mediated inhibition of VCAM-1 expression and leukocyte adhesion. Thus, our study identifies TSP-1:CD47 interaction as a molecular pathway that modulates IL-17-mediated VCAM-1 expression, contributing to its anti-inflammatory effect in chronic inflammatory conditions.
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影响因子:
2.8
作者:
Chen, Chong;Zhang, Qiuyang;Liu, Sen;Parajuli, Keshab R.;Qu, Yine;Mei, Jiandong;Chen, Zhiquan;Zhang, Hui;Khismatullin, Damir B.;You, Zongbing
通讯作者:
You, Zongbing
影响因子:
4.8
作者:
Narizhneva, NV;Razorenova, OV;Byzova, TV
通讯作者:
Byzova, TV
影响因子:
4.4
作者:
Schwab, Nicholas;Schneider-Hohendorf, Tilman;Wiendl, Heinz
通讯作者:
Wiendl, Heinz
影响因子:
20.1
作者:
Liu Z;Morgan S;Ren J;Wang Q;Annis DS;Mosher DF;Zhang J;Sorenson CM;Sheibani N;Liu B
通讯作者:
Liu B
影响因子:
3.4
作者:
Contreras-Ruiz, Laura;Mir, Fayaz A.;Masli, Sharmila
通讯作者:
Masli, Sharmila