Fibronectin and α5 integrin regulate keratinocyte cell cycling -: A mechanism for increased fibronectin potentiation of T cell lymphokine-driven keratinocyte hyperproliferation in psoriasis

被引:60
作者
Bata-Csorgo, Z
Cooper, KD
Ting, KM
Voorhees, JJ
Hammerberg, C
机构
[1] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Dermatol, Cleveland, OH 44106 USA
[2] Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI 48109 USA
[3] Vet Adm Med Ctr, Dept Dermatol, Cleveland, OH 44106 USA
关键词
psoriasis; fibronectin; alpha; 5; beta; 1; integrin; keratinocytes; T lymphokines;
D O I
10.1172/JCI171
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
In addition to being T lymphocyte-driven, psoriasis may be due in part to abnormal integrin expression. Normal-appearing (uninvolved) skin from psoriatic patients was examined to determine whether altered fibronectin or its receptor expression is detectable before development of psoriatic lesions. In contrast to skin from normal subjects, we detect by immunofluorescence the abnormal presence of plasma fibronectin in the basal cell layer of the epidermis of psoriatic uninvolved skin. Furthermore, increased fibronectin exposure superinduces the in vitro cell cycle induction and expansion of psoriatic nonlesional keratinocytes in response to a cocktail of T cell lymphokines. Fibronectin alone also appeared to increase cell cycle entry among uninvolved but not normal keratinocytes. Concordantly, the alpha 5 integrin fibronectin receptor, but not alpha 2 or alpha 3, is overexpressed in the in vivo nonlesional psoriatic epidermis. The involvement of alpha 5 beta 1 in the early outgrowth of clonogenic keratinocytes in the ex vivo culture was demonstrated by the ability of anti-alpha 5 mAb to inhibit keratinocyte growth on fibronectin. Thus, the fibronectin receptor appears to be one of the components required for the development of the hyperresponsiveness of psoriatic keratinocytes to signals for proliferation provided by lymphokines produced by intralesional T lymphocytes in psoriasis.
引用
收藏
页码:1509 / 1518
页数:10
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