HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Skin-penetrating methotrexate alleviates imiquimod-induced psoriasiform dermatitis via decreasing IL-17-producing gamma delta T cells.

Abstract
Accumulating evidence has shown that the Toll-like receptor 7 agonist imiquimod (IMQ) induces psoriasiform skin inflammation in mice and that this inflammation is dependent on the IL-23/IL-17 axis. Moreover, it has been demonstrated that the main source of IL-17 is not Th17 but is dermal gamma delta (γδ) T cells in mouse psoriasiform skin. Recent advances in the understanding of immunopathogenesis of psoriasis led to an alteration in the treatment paradigm to the use of highly efficacious biologics. However, their high cost impedes the extensive use of these agents. Thus, inexpensive and safe medications are still considered valuable. In this study, we introduce the therapeutic efficacy of a newly formulated methotrexate (MTX), a chemical conjugate of MTX with cell permeable peptide, for the treatment of psoriasis. Topically applied skin-penetrating (SP)-MTX reduced the psoriasiform skin phenomenon, epidermal thickness and infiltrating immune cells into the dermis. IL-17A-producing dermal γδ T cells in the cellular infiltrate that contribute IL-23/IL-17 axis were well abrogated by SP-MTX. Furthermore, SP-MTX had no toxic effects on liver, kidney or myeloid cells, unlike systemic administration of MTX. In conclusion, topically applied SP-MTX ameliorated psoriasiform skin inflammation in mice with the criteria of clinical phenomenon, histopathology and immunology, without inducing systemic toxic effects.
AuthorsDashlkhumbe Byamba, Do Young Kim, Dae-Suk Kim, Tae-Gyun Kim, Hyunjoong Jee, Sung Hee Kim, Tae-Yoon Park, Sang-Hwa Yang, Sang-Kyou Lee, Min-Geol Lee
JournalExperimental dermatology (Exp Dermatol) Vol. 23 Issue 7 Pg. 492-6 (Jul 2014) ISSN: 1600-0625 [Electronic] Denmark
PMID24824846 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Chemical References
  • Aminoquinolines
  • CD11c Antigen
  • Cytokines
  • DNA, Complementary
  • Interleukin-17
  • Interleukin-23
  • Peptides
  • Imiquimod
  • Methotrexate
Topics
  • Aminoquinolines (adverse effects)
  • Animals
  • CD11c Antigen (metabolism)
  • CD4-Positive T-Lymphocytes (cytology)
  • Cytokines (metabolism)
  • DNA, Complementary (metabolism)
  • Dermatitis (drug therapy, etiology)
  • Female
  • Imiquimod
  • Inflammation
  • Interleukin-17 (metabolism)
  • Interleukin-23 (metabolism)
  • Methotrexate (administration & dosage)
  • Mice
  • Mice, Inbred BALB C
  • Peptides (chemistry)
  • Permeability
  • Psoriasis (chemically induced, drug therapy, immunology)
  • Skin (drug effects, immunology, pathology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: