Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-2-22
pubmed:abstractText
Although methotrexate (MTX) is one of the most clinically effective therapies employed to treat psoriasis, the mechanism by which low-dose MTX acts to modulate the hyperplasia of psoriasis, leading to the restoration of clinically normal skin, is only partially understood. MTX has been considered a cytotoxic agent that mediates its effect primarily on proliferating or cycling epidermal cells. Recently, proliferating lymphoid cells have been identified in psoriatic lesions, raising the possibility that proliferating lymphoid cells could be another target cell that is killed by MTX. In this study, we examined the growth-inhibitory and cytotoxic effects of MTX on proliferating lymphoid cells [THP-1 (macrophage), and MOLT-4 (T cell)], epithelial cells (HeLa, and HaCat), and normal human keratinocytes (NHK) in vitro. The proliferating cells were exposed to MTX for 24 h, and placed in fresh media to mimic the transient MTX blood levels that result from once-weekly therapy. THP-1 and MOLT-4 were found to be 10-100 times more sensitive to the cytotoxic effects of MTX than were HeLa and HaCat, and more than 1000 times more sensitive than primary human keratinocytes. At MTX concentrations that would be expected to occur in vivo during once-weekly therapy, a large percentage (> 95%) of proliferating lymphoid targets would be killed, and only a small percentage (< 10%) of proliferating epidermal cells would be affected. This in vitro data suggests that in psoriasis proliferating lymphoid cells are more likely than epithelial cells to be a major cellular target of MTX in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
183-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate.
pubmed:affiliation
Department of Dermatology, University of California, Irvine.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't