| First Author | Velasco P | Year | 2009 |
| Journal | J Invest Dermatol | Volume | 129 |
| Issue | 8 | Pages | 2022-30 |
| PubMed ID | 19194474 | Mgi Jnum | J:152510 |
| Mgi Id | MGI:4358858 | Doi | 10.1038/jid.2008.447 |
| Citation | Velasco P, et al. (2009) The angiogenesis inhibitor thrombospondin-1 inhibits acute cutaneous hypersensitivity reactions. J Invest Dermatol 129(8):2022-30 |
| abstractText | There is increasing evidence that vascular remodeling and endothelial cell activation promote acute and chronic inflammation. Thrombospondin 1 (TSP-1) is a potent endogenous angiogenesis inhibitor thought to play an important role in maintaining cutaneous vascular quiescence. We first investigated TSP-1 expression in human and contact hypersensitivity (CHS) reactions and found that TSP-1 was upregulated in the inflamed skin of patients and in mice. To elucidate the function of TSP-1 in cutaneous inflammation, we induced CHS reactions in the skin of mice with targeted epidermal TSP-1 overexpression in TSP-1-deficient mice and in wild-type mice. We found decreased edema formation, angiogenesis, and inflammatory infiltrate in the inflamed skin of TSP-1 transgenic mice. Conversely, TSP-1-deficient mice exhibited an enhanced and prolonged inflammation, characterized by increased edema formation, enhanced vascular remodeling, and increased neutrophilic infiltrate, when compared with wild-type mice. Moreover, we found strong upregulation of the proinflammatory cytokines IL-1beta, macrophage inflammatory protein 2, and tumor necrosis factor-alpha in the inflamed skin of TSP-1-deficient mice. Our results indicate that TSP-1 downregulates cutaneous delayed-type hypersensitivity reactions by acting on several distinct pathways mediating skin inflammation. |
