Methotrexate treatment provokes apoptosis of proliferating keratinocyte in psoriasis patients

被引:0
作者
Tamilselvi Elango
Anand Thirupathi
Swapna Subramanian
Purushoth Ethiraj
Haripriya Dayalan
Pushpa Gnanaraj
机构
[1] SRM University,Department of Medical Research, SRM Medical College, Hospital and Research Centre
[2] Universidade do Extremo Sul Catarinense,Laboratory of Physiology and Biochemistry of Exercise, PPGCS
[3] SRM University,Department of Biochemistry, SRM Medical College, Hospital and Research Centre
[4] Rajalakshmi Engineering College,Department of Biotechnology
[5] SRM University,Department of Dermatology, SRM Medical College, Hospital and Research Centre
来源
Clinical and Experimental Medicine | 2017年 / 17卷
关键词
Methotrexate; Caspase-9; Cytochrome ; c-FLIP; Psoriasis; NFκBp65;
D O I
暂无
中图分类号
学科分类号
摘要
Psoriasis is a chronic inflammatory skin disease characterized by hyper proliferation of keratinocytes. Recent data show that the epidermis thickening in psoriasis may be related to imbalance of homeostasis caused by abnormal apoptotic process. Maintenance of keratinocyte apoptotic process is very important in psoriasis. Methotrexate (MTX) has been used for many years to restore the normal skin in psoriasis condition. However, the exact mechanism of MTX in psoriasis condition is poorly understood. The aim of this study was to examine the role of MTX on keratinocyte apoptosis pathway in psoriasis patients. A total of 58 psoriasis vulgaris patients were recruited for this study. Nonlesional skin biopsies served as control. Skin biopsies of psoriatic patients were collected and analyzed for cytosolic, mitochondria and total cytochrome c by ELISA. Expression of caspase-9, NFκBp65, pAkt1 by western blot, real-time PCR and immunohistochemical analysis of c-FLIP protein was analyzed in nonlesional and lesional skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment. After MTX treatment, a significant increase in cytochrome c was observed when compared with before MTX treatment in psoriasis patients (p < 0.001). Protein and gene expression of cleaved caspase-9 were significantly increased after MTX treatment, whereas the expression of Bcl-xL, c-FLIP, NFκBp65, pAkt1 significantly downregulated after MTX treatment. In conclusion, these results showed that intrinsic apoptotic pathway induced by MTX eventually adds the beneficial therapeutic role of MTX in psoriasis by controlling the acanthosis.
引用
收藏
页码:371 / 381
页数:10
相关论文
共 191 条
  • [1] Gonzalez S(1999)Characterization of psoriasis in vivo by reflectance confocal microscopy J Med 30 337-356
  • [2] Rajadhyaksha M(2008)Comparative study of histopathological and immunohistochemical findings in skin biopsies from patients with psoriasis before and after treatment with acitretin J Cutan Pathol 35 302-310
  • [3] Rubinstein G(1999)Apoptosis and skin Eur J Dermatol 9 413-426
  • [4] Anderson RR(2006)Keratinocyte apoptosis in epidermal development and disease J Invest Dermatol 126 243-257
  • [5] Werner B(2001)FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis Mol Cell Biol 21 8247-8254
  • [6] Bresch M(2001)Regulation of lymphocyte proliferation and death by FLIP Nat Rev Immunol 1 50-58
  • [7] Brenner FM(2000)The caspase-8 inhibitor FLIP promotes activation of NF-kappaB and Erk signaling pathways Curr Biol 10 640-648
  • [8] Lima HC(2000)Apoptosis in established and healing psoriasis Dermatology 200 314-316
  • [9] Teraki Y(2006)Programmed cell death of keratinocytes in infliximab-treated plaque-type psoriasis Br J Dermatol 154 460-466
  • [10] Shiohara T(1993)Increased superoxide anion production in dermal fibroblasts of psoriatic patients Skin Pharmacol 6 253-258