We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Transforming Growth Factor-β Receptor Binding and Function Are Decreased in Psoriatic Dermal Endothelium.
- Authors
Cai, Jian-Ping; Falanga, Vincent; Taylor, J. Richard; Chin, Yee-Hon
- Abstract
T lymphocytes adhere to dermal microvascular endothelial cells (DMEC) as the first step in their emigration from the blood vasculature into diseased skin. Earlier studies have shown that the adhesiveness of cultured DMEC from normal skin for lymphocytes can be blocked by transforming growth factor-E1 (TGF-βl). In contrast, TGF-β1 has no effect on the adhesive properties of DMEC from psoriatic plaques, and this response is attenuated by the addition of interleukin-4 (IL-4). In the present study, we show that both TGF-β1 and TGF-β2, and to a lesser extent TGF-β3 isoforms block the ability of normal but not psoriatic DMEC to bind lymphocytes. Pretreatment with TGF-β1 selectively inhibited the tumor necrosis factor-α (TNF-α)-stimulated expression of E-selectin on normal DMEC but had no effect on psoriatic DMEC. Scatchard analysis revealed both low- and high-affinity receptors on normal DMEC. The baseline number of high-affinity TGF-β receptors was significantly reduced on psoriatic DMEC, whereas IL-4 treatment of DMEC altered the binding affinity but not the number of receptors. The protein and mRNA transcripts of type I and type II TGF-β receptor genes were detectable in psoriatic DMEC. A reduction in the autophosphorylation of the TGF-β type II receptor protein, a constitutively active serine/threonine kinase, however, was detected in psoriatic DMEC. These <em>in vitro</em> findings suggest that reduction of TGF-β receptor expression and function may contribute to lymphocyte infiltration into psoriatic plaques in vivo by allowing dermal microvascular endothelium to escape from the negative regulation by TGF-β.
- Subjects
LYMPHOCYTES; SKIN; INTERLEUKINS; MESSENGER RNA; PHOSPHORYLATION; TUMORS
- Publication
Journal of Investigative Dermatology, 1996, Vol 106, Issue 2, p225
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12340553