Ultrastructural findings and tumor necrosis factor-alpha and intercellular adhesion molecule-1 expression in psoriasis patients before and after oral cyclosporin A therapy

被引:5
作者
Esrefoglu, Mukaddes [1 ]
Gul, Mehmet
Seyhan, Muammer
机构
[1] Inonu Univ, Fac Med, Dept Histol & Embryol, TR-44280 Malatya, Turkey
[2] Inonu Univ, Fac Med, Dept Dermatol, TR-44280 Malatya, Turkey
关键词
basement membrane; ICAM-1; psoriasis; TNF-alpha; transmission electron microscopy;
D O I
10.1080/01013120500406616
中图分类号
TH742 [显微镜];
学科分类号
摘要
Elevated levels of proinflammatory cytokines, including tumor necrosis factor-alpha, are found in skin lesions and plasma of patients with psoriasis. Clinical improvement of psoriasis with cyclosporin A treatment is accompanied by downmodulation of proinflammatory epidermal cytokines. In this study to determine the effects of cyclosporin A on the ultrastructural changes and tumor necrosis factor-alpha and intercellular adhesion molecule-1 expression in psoriasis, biopsy specimens before and after cyclosporin A treatment were evaluated ultrastructurally and immunohistochemically. Ten patients were given 3-7.5 mg/kg oral cyclosporin A for 6 months. Before and after treatment full thickness of 4-mm punch biopsies were obtained from patients and from 6 healthy volunteers. Samples were processed for electron microscopic and immunohistochemical evaluation. The treatment was well tolerated with complete clinical improvement. The ultrastructural changes such as reduction of tonofilaments, dilatation of intercellular space, and interruption in lamina densa were recovered by cyclosporin A treatment. The increased staining intensity of tumor necrosis factor-alpha and intercellular adhesion molecule-1 on epidermal keratinocytes and endothelial cells was reduced after cyclosporin A therapy. Cyclosporin A treatment results in total normalization of the electron microscopic picture of psoriasis and its beneficial effect depends on the direct inhibition of tumor necrosis factor-alpha and consequently intercellular adhesion molecule-1.
引用
收藏
页码:95 / 102
页数:8
相关论文
共 45 条
[1]   ADHESION MOLECULES AND INFLAMMATORY INJURY [J].
ALBELDA, SM ;
SMITH, CW ;
WARD, PA .
FASEB JOURNAL, 1994, 8 (08) :504-512
[2]   A SUBSET OF MACROPHAGES LOCATED ALONG THE BASEMENT-MEMBRANE (LINING CELLS) IS A CHARACTERISTIC HISTOPATHOLOGICAL FEATURE OF PSORIASIS [J].
BOEHNCKE, WH ;
WORTMANN, S ;
KAUFMANN, R ;
MIELKE, V ;
STERRY, W .
AMERICAN JOURNAL OF DERMATOPATHOLOGY, 1995, 17 (02) :139-144
[3]   Alterations in ICAM-1 and ELAM-1 expression in psoriatic lesions following various treatments [J].
Danno, K ;
Kaji, A ;
Mochizuki, T .
JOURNAL OF DERMATOLOGICAL SCIENCE, 1996, 13 (01) :49-55
[4]  
DAS PK, 1994, ACTA DERM-VENEREOL, V74, P21
[5]   CYCLOSPORINE-A RAPIDLY INHIBITS EPIDERMAL CYTOKINE EXPRESSION IN PSORIASIS LESIONS, BUT NOT IN CYTOKINE-STIMULATED CULTURED KERATINOCYTES [J].
ELDER, JT ;
HAMMERBERG, C ;
COOPER, KD ;
KOJIMA, T ;
NAIR, RP ;
ELLIS, CN ;
VOORHEES, JJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1993, 101 (06) :761-766
[6]   CYCLOSPORINE FOR PLAQUE-TYPE PSORIASIS - RESULTS OF A MULTIDOSE, DOUBLE-BLIND TRIAL [J].
ELLIS, CN ;
FRADIN, MS ;
MESSANA, JM ;
BROWN, MD ;
SIEGEL, MT ;
HARTLEY, AH ;
ROCHER, LL ;
WHEELER, S ;
HAMILTON, TA ;
PARISH, TG ;
ELLISMADU, M ;
DUELL, E ;
ANNESLEY, TM ;
COOPER, KD ;
VOORHEES, JJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (05) :277-284
[7]   Cyclosporine in severe psoriasis: Results of a meta-analysis in 579 patients [J].
Faerber L. ;
Braeutigam M. ;
Weidinger G. ;
Mrowietz U. ;
Christophers E. ;
Schulze H.J. ;
Mahrle G. ;
Meffert H. ;
Drechsler S. .
American Journal of Clinical Dermatology, 2001, 2 (1) :41-47
[8]   STIMULATION OF THE ADHERENCE OF NEUTROPHILS TO UMBILICAL VEIN ENDOTHELIUM BY HUMAN RECOMBINANT TUMOR-NECROSIS-FACTOR [J].
GAMBLE, JR ;
HARLAN, JM ;
KLEBANOFF, SJ ;
VADAS, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (24) :8667-8671
[9]  
GEARING A J H, 1990, Cytokine, V2, P68, DOI 10.1016/1043-4666(90)90045-U
[10]  
Gisondi Paolo, 2004, Current Drug Targets - Inflammation and Allergy, V3, P175, DOI 10.2174/1568010043343903