title: Methotrexate treatment provokes apoptosis of proliferating keratinocyte in psoriasis patients.
abstract: 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.
authors.affiliation: Department of Medical Research, SRM Medical College, Hospital and Research Centre, SRM University, Kattankulathur, Tamilnadu, 603203, India. tami24684@gmail.com.
authors.forename: Tamilselvi
authors.initials: T
authors.lastname: Elango
authors.affiliation: Laboratory of Physiology and Biochemistry of Exercise, PPGCS, Universidade do Extremo Sul Catarinense, Criciúma, SC, 88806-000, Brazil.
authors.forename: Anand
authors.initials: A
authors.lastname: Thirupathi
authors.affiliation: Department of Biochemistry, SRM Medical College, Hospital and Research Centre, SRM University, Kattankulathur, Tamilnadu, 603203, India.
authors.forename: Swapna
authors.initials: S
authors.lastname: Subramanian
authors.affiliation: Department of Medical Research, SRM Medical College, Hospital and Research Centre, SRM University, Kattankulathur, Tamilnadu, 603203, India.
authors.forename: Purushoth
authors.initials: P
authors.lastname: Ethiraj
authors.affiliation: Department of Biotechnology, Rajalakshmi Engineering College, Thandalam, Chennai, Tamilnadu, 602105, India.
authors.forename: Haripriya
authors.initials: H
authors.lastname: Dayalan
authors.affiliation: Department of Dermatology, SRM Medical College, Hospital and Research Centre, SRM University, Kattankulathur, Tamilnadu, 603203, India.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Gnanaraj
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000473:pathology*; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D008727:Methotrexate
keywords: Caspase-9; Cytochrome c; Methotrexate; NFκBp65; Psoriasis; c-FLIP