Methotrexate normalized keratinocyte activation cycle by overturning abnormal keratins as well as deregulated inflammatory mediators in psoriatic patients.
BACKGROUND
In psoriatic skin, epidermal keratinocytes undergo deregulated inflammatory response that leads to prolonged expression of inflammatory mediators as well as abnormal keratins. Methotrexate (MTX) is an immunosuppressive agent used as a standard drug to treat severe psoriasis. The aim of the study is to find the pharmacological effect of MTX on abnormal keratin and deregulated inflammatory mediators.


METHODS
Fifty-eight psoriasis vulgaris patients were recruited for this study. Skin biopsies of psoriatic patients were collected and analyzed for activation signal such as TNF-α and IFN-γ and deactivation signal such as TGF-β1. Also, protein and gene expression of normal keratins K14 and K10 and abnormal keratins K16 and K17 were analyzed in skin biopsies before (day 0) and after (at the end of 6 and 12 weeks) MTX treatment.


RESULTS
Results show a significant decrease in tissue TNF-α and IFN-γ and increase in TGF-β1 after MTX treatment when compared with before MTX treatment in psoriasis patients (p<0.001). Protein and gene expression of K14, K16 and K17 decreased after MTX treatment, whereas the expression of differentiation marker K10 increased after MTX treatment.


CONCLUSIONS
MTX resolves deregulated inflammatory markers and maintains normal keratin phenotype on hyperproliferating KC, thereby controlling acanthosis in psoriasis patients.
Department of Medical Research, SRM Medical College, Hospital and Research Centre, Kattankulathur 603203, Tamilnadu, India. Electronic address: tami24684@gmail.com.
Tamilselvi
T
Elango
Laboratory of Physiology and Biochemistry of Exercise, PPGCS, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Anand
A
Thirupathi
Department of Biochemistry, SRM Medical College, Hospital and Research Centre, Kattankulathur 603203, Tamilnadu, India.
Swapna
S
Subramanian
Department of Biotechnology, Rajalakshmi Engineering College, Thandalam, Chennai 602105, Tamilnadu, India.
Haripriya
H
Dayalan
Department of Dermatology, SRM Medical College, Hospital and Research Centre, Kattankulathur 603203, Tamilnadu, India.
Pushpa
P
Gnanaraj
D000293:Adolescent; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D007633:Keratins / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D018836:Inflammation Mediators; D007633:Keratins; D008727:Methotrexate
Interferon-γ; Keratin 16; Keratin 17; Methotrexate; Transforming growth factor-β(1)