Regulation Of Epidermal Proliferation And Differentiation In Psoriasis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111132/1/jde01861.pd

Consensus conference on cyclosporin A microemulsion for psoriasis, June 1996

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75561/1/j.1365-2133.1996.d01-1061.x.pd

Molecular mechanisms of retinoid actions in skin

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154473/1/fsb2010009001.pd

THE EPIDERMIS AND CYCLIC AMP

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73687/1/j.1365-2133.1974.tb06390.x.pd

Leukotrienes B 4 , C 4 and D 4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Leukotrienes in psoriatic skin lesions are potent mediators of inflammation. We have studied the capacity of leukotrienes to stimulate the DNA synthesis of cultured human epidermal keratinocytes. At concentrations ranging from 10 −12 to 10 −8 M, LTB 4 produced a 100% increase of DNA synthesis determined both as the incorporation of [ 3 H] thymidine and as the labelling index. In comparison, LTB 4 had no effect on the DNA synthesis of dermal fibroblast cultures. 5S, 12S-LTB 4 and 5S, 12S-all-trans-LTB 4 did not change the DNA synthesis of keratinocytes, but the effect of LTB 4 was abolished in the presence of 5S, 12S-all- trans HLTB 4 . Being less potent than LTB 4 the peptidoleukotrienes (LTC 4 , LTD 4 ) also stimulated keratinocyte DNA synthesis. The effect of the peptidoleukotrienes, but not of LTB 4 , was antagonized by EPL 55712. These results show that leukotrienes B 4 , C 4 and D 4 exert potent and stereospecific mitogenic effects on cultured human keratinocytes. The presence of these arachidonic acid metabolites in psoriatic skin lesions may be pertinent to both inflammation and aberrant epidermal growth in psoriasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74813/1/j.1365-2133.1985.tb02043.x.pd

CUTANEOUS ANGIITIS (VASCULITIS)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66185/1/j.1365-4362.1978.tb06119.x.pd

Retinoic acid induces expression of PA-FABP (psoriasis-associated fatty acid-binding protein) gene in human skin in vivo but not in cultured skin cells

: PA-FABP (psoriasis-associated fatty acid binding protein) is a new member of a group of low-molecular-weight proteins that are highly up regulated in psoriatic skin and that share similarity to fatty acid-binding proteins. In this study we demonstrate that PA-FABP transcripts are expressed in human skin in vivo and that topical application of 0.05% retinoic acid (RA) cream results in a rapid induction of PA-FABP transcripts following treatment for 16 hours and persists at increasing levels after 48 and 96 h of RA treatment. The PA-FABP mRNA response to RA was reduced by approximately 50% when patients concurrently were treated with RA and 0.025% clobelasol propionate (CLO) for 48 and 96 h, whereas treatment with CLO alone resulted in PA-FABP transcript levels not significantly different from vehicle-treated skin. When comparing the effects of a well-known irritant, sodium lauryl sulfate (SLS), to those of RA and its vehicle, 0.05% RA cream but not 2% SLS in RA vehicle caused PA-FABP mRNA induction after 16 h. SLS treatment of human skin for 96 h caused a slight increase in PA-FABP transcripts, but markedly less than that observed in response to RA treatment. Incubation of cultured human keratinocytes or skin fibroblasts with RA for up to 48 h did not significantly induce PA-FABP transcripts. Expression of PA-FABP message in keratinocytes was observed to be induced by calcium and fetal calf serum (FCS), while tetra-decanoyl phorbol acetate (TPA) caused little or no induction. Taken together, the marked inducibility of the PA-FABP gene is compatible with the possibility that this gene might be important in RA-mediated regulation of human skin growth and differentiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72938/1/j.1600-0625.1994.tb00279.x.pd

Retinoic Acid Isomers Applied to Human Skin in Vivo Each Induce a 4-Hydroxylase That Inactivates Only Trans Retinoic Acid

Application of all-trans retinoic acid to human skin for 4 d under occlusion produces a marked increase in retinoic acid 4-hydroxylase activity. In this study, the possible induction of other hydroxylases in response to 9-cis and 13-cis retinoic acid applications to adult human skin in vivo was determined. Application of 0.1% all-trans, 0.1% 9-cis, and 0.1% 13-cis retinoic acid to human skin for 2 d resulted in induction of only all-trans retinoic acid 4-hydroxylase activity. The 4-hydroxylase activity in microsomes from the treated tissue ranged from 383 ± 46 to 531 ± 59pg of 4-hydroxy all-trans retinoic acid formed/min/mg protein (n = 6). These same preparations were unable to use 9-cis or 13-cis retinoic acid as substrate for the hydroxylation reaction. Extraction of the retinoic acid isomers from epidermis 48h after application of 0.1% solution of each isomer yielded significant amounts of all-trans retinoic acid (36-72%) regardless of the isomer applied. The all-trans isomer produced by isomerization of both 9-cis and 13-cis retinoic acids is the likely inducer of the 4-hydroxylase. All-trans retinol and all-trans retinal were unable to compete with all-trans retinoic acid as substrate for 4-hydroxylase enzyme. The 4-hydroxylase induced in response to pharmacological doses of retinoic acids is specific for the all-trans isomer. The inability of 9-cis or 13-cis retinoic acid to induce their own hydroxylation and inactivation or act as substrate for the 4-hydroxylase in skin may have considerable implications in light of the clinical use of retinoids in the treatment of various diseases including cancers

Age‐associated reduction of cellular spreading/mechanical force up‐regulates matrix metalloproteinase‐1 expression and collagen fibril fragmentation via c‐Jun/ AP ‐1 in human dermal fibroblasts

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109644/1/acel12265.pd