Intercellular adhesion molecule-1 deficiency attenuates the development of skin fibrosis in tight-skin mice.

Published

Journal Article

The tight-skin (TSK/+) mouse, a genetic model for systemic sclerosis, develops cutaneous fibrosis. Although a fibrillin 1 gene mutation and immunological abnormalities have been demonstrated, the roles of adhesion molecules have not been investigated. To directly assess roles of adhesion molecules in skin fibrosis, TSK/+ mice lacking L-selectin and/or ICAM-1 were generated. The deficiency of ICAM-1, but not L-selectin, significantly suppressed ( approximately 48%) the development of skin sclerosis in TSK/+ mice. Similarly, ICAM-1 antisense oligonucleotides inhibited skin fibrosis in TSK/+ mice. Although T cell infiltration was modest into the skin of TSK/+ mice, ICAM-1 deficiency down-regulated this migration, which is consistent with the established roles of endothelial ICAM-1 in leukocyte infiltration. In addition, altered phenotype or function of skin fibroblasts was remarkable and dependent on ICAM-1 expression in TSK/+ mice. ICAM-1 expression was augmented on TSK/+ dermal fibroblasts stimulated with IL-4. Although growth or collagen synthesis of TSK/+ fibroblasts cultured with IL-4 was up-regulated, it was suppressed by the loss or blocking of ICAM-1. Collagen expression was dependent on the strain of fibroblasts, but not on the strain of cocultured T cells. Thus, our findings indicate that ICAM-1 expression contributes to the development of skin fibrosis in TSK/+ mice, especially via ICAM-1 expressed on skin fibroblasts.

Full Text

Duke Authors

Cited Authors

  • Matsushita, Y; Hasegawa, M; Matsushita, T; Fujimoto, M; Horikawa, M; Fujita, T; Kawasuji, A; Ogawa, F; Steeber, DA; Tedder, TF; Takehara, K; Sato, S

Published Date

  • July 2007

Published In

Volume / Issue

  • 179 / 1

Start / End Page

  • 698 - 707

PubMed ID

  • 17579093

Pubmed Central ID

  • 17579093

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.179.1.698

Language

  • eng