Potential efficacy of imiquimod on immunity-related cytokines in murine skin in vivo and in human Langerhans cells in vitro

被引:5
作者
Miao, Xu [2 ]
Luo, Dan [1 ]
Min, Wei [3 ]
Lin, Xiangfei [1 ]
Wang, Daguang [1 ]
Xu, Yang [1 ]
Wu, Di [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Dermatol, Nanjing 210029, Jiangsu, Peoples R China
[2] Nantong Univ, Affiliated Hosp 2, Dept Dermatol, Nantong, Peoples R China
[3] Soochow Univ, Dept Dermatol, Affiliated Hosp 1, Suzhou, Peoples R China
基金
中国国家自然科学基金;
关键词
DENDRITIC CELLS; MESSENGER-RNA; HUMAN KERATINOCYTES; TOPICAL APPLICATION; RESPONSE MODIFIER; 5-PERCENT CREAM; FLOW-CYTOMETRY; OPEN-LABEL; CRYOSURGERY; CARCINOMA;
D O I
10.1111/j.1365-4632.2011.05382.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Introduction Imiquimod, an immune-response modifier, has been proven to be clinically effective in the treatment of viral infections and skin cancers, but its mechanism of action remains poorly understood. This study aimed to assess the effects of imiquimod on the expression of three immunity-related cytokines, TNF-a, IL-1 beta, and IL-6. Materials and methods Female BALB/C mice were treated for seven days with topical 1% imiquimod cream; they were then killed and skin samples were snap-frozen. In the in vitro studies, both purified LCs and HaCaT cells were incubated with 5 mu g/ml imiquimod for four hours. In all samples, the mRNA levels of TNF-a, IL-1 beta, and IL-6 were then detected by reverse transcription polymerase chain reaction, and the secretion levels were determined by an enzyme-linked immunosorbent assay. Results Imiquimod upregulated the mRNA and protein expression levels of TNF-a, IL-1 beta, and IL-6 in the skin of imiquimod-treated BALB/C mice and in human LCs, compared with untreated controls (P < 0.05). However, there was no significant difference in the expression of these cytokines in imiquimod-treated and untreated HaCaT cells. Conclusions These findings indicate that imiquimod increased the expression of TNF-a, IL-1 beta, and IL-6 in skin and that the target cell of imiquimod may be the LCs but is unlikely to be the epidermal keratinocytes.
引用
收藏
页码:1116 / 1122
页数:7
相关论文
共 39 条
[1]   CYTOKINE MODULATION OF KERATINOCYTE CYTOKINES [J].
ANSEL, J ;
PERRY, P ;
BROWN, J ;
DAMM, D ;
PHAN, T ;
HART, C ;
LUGER, T ;
HEFENEIDER, S .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1990, 94 (06) :S101-S107
[2]   Cryosurgery during topical imiquimod:: a successful combination modality for lentigo maligna [J].
Bassukas, I. D. ;
Gamvroulia, C. ;
Zioga, A. ;
Nomikos, K. ;
Fotika, C. .
INTERNATIONAL JOURNAL OF DERMATOLOGY, 2008, 47 (05) :519-521
[3]   Interleukin-15 mRNA is expressed by human keratinocytes, Langerhans cells, and blood-derived dendritic cells and is downregulated by ultraviolet B radiation [J].
Blauvelt, A ;
Asada, H ;
KlausKovtun, V ;
Altman, DJ ;
Lucey, DR ;
Katz, SI .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1996, 106 (05) :1047-1052
[4]   The imidazoquinolines, imiquimod and R-848, induce functional, but not phenotypic, maturation of human epidermal Langerhans' cells [J].
Burns, RP ;
Ferbel, B ;
Tomai, M ;
Miller, R ;
Gaspari, AA .
CLINICAL IMMUNOLOGY, 2000, 94 (01) :13-23
[5]   FLOW-CYTOMETRY SORTING OF UNLABELED EPIDERMAL LANGERHANS CELLS USING FORWARD AND ORTHOGONAL LIGHT SCATTER PROPERTIES [J].
CORDIER, G ;
DEZUTTERDAMBUYANT, C ;
LEFEBVRE, R ;
SCHMITT, D .
JOURNAL OF IMMUNOLOGICAL METHODS, 1985, 79 (01) :79-88
[6]   Multiple keratoacanthomas as an untoward response to imiquimod therapy for actinic keratoses [J].
D'Addario, Stephen ;
Carrington, Patrick R. .
ACTA DERMATO-VENEREOLOGICA, 2006, 86 (04) :366-367
[7]   Imiquimod and resiquimod as novel immunomodulators [J].
Dockrell, DH ;
Kinghorn, GR .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2001, 48 (06) :751-755
[8]   Host-derived langerhans cells persist after MHC-matched allografting independent of donor T cells and critically influence the alloresponses mediated by donor lymphocyte infusions [J].
Durakovic, Nadira ;
Bezak, Karl B. ;
Skarica, Mario ;
Radojcic, Vedran ;
Fuchs, Ephraim J. ;
Murphy, George F. ;
Luznik, Leo .
JOURNAL OF IMMUNOLOGY, 2006, 177 (07) :4414-4425
[9]   Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application [J].
Gaitanis, G. ;
Nomikos, K. ;
Vava, E. ;
Alexopoulos, E. C. ;
Bassukas, I. D. .
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY, 2009, 23 (12) :1427-1431
[10]   Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from two phase III, randomized, vehicle-controlled studies [J].
Geisse, J ;
Caro, I ;
Lindholm, J ;
Golitz, L ;
Stampone, P ;
Owens, M .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2004, 50 (05) :722-733