Linked Life Data

12542530

Source:http://linkedlifedata.com/resource/pubmed/id/12542530

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-1-24
pubmed:abstractText
Activators of liver X receptors (LXR) stimulate epidermal differentiation and development, but inhibit keratinocyte proliferation. In this study, the anti-inflammatory effects of two oxysterols, 22(R)-hydroxy-cholesterol (22ROH) and 25-hydroxycholesterol (25OH), and a nonsterol activator of LXR, GW3965, were examined utilizing models of irritant and allergic contact dermatitis. Irritant dermatitis was induced by applying phorbol 12-myristate-13-acetate (TPA) to the surface of the ears of CD1 mice, followed by treatment with 22ROH, 25OH, GW3965, or vehicle alone. Whereas TPA treatment alone induced an approximately 2-fold increase in ear weight and thickness, 22ROH, 25OH, or GW3965 markedly suppressed the increase (greater than 50% decrease), and to an extent comparable to that observed with 0.05% clobetasol treatment. Histology also revealed a marked decrease in TPA-induced cutaneous inflammation in oxysterol-treated animals. As topical treatment with cholesterol did not reduce the TPA-induced inflammation, and the nonsterol LXR activator (GW3965) inhibited inflammation, the anti-inflammatory effects of oxysterols cannot be ascribed to a nonspecific sterol effect. In addition, 22ROH did not reduce inflammation in LXRbeta-/- or LXRalphabeta-/- animals, indicating that LXRbeta is required for this anti-inflammatory effect. 22ROH also caused a partial reduction in ear thickness in LXRalpha-/- animals, however (approximately 50% of that observed in wild-type mice), suggesting that this receptor also mediates the anti-inflammatory effects of oxysterols. Both ear thickness and weight increased (approximately 1.5-fold) in the oxazolone-induced allergic dermatitis model, and 22ROH and GW3965 reduced inflammation by approximately 50% and approximately 30%, respectively. Finally, immunohistochemistry demonstrated an inhibition in the production of the pro-inflammatory cytokines interleukin-1alpha and tumor necrosis factor alpha in the oxysterol-treated sites from both TPA- and oxazolone-treated animals. These studies demonstrate that activators of LXR display potent anti-inflammatory activity in both irritant and allergic contact models of dermatitis, requiring the participation of both LXRalpha and LXRbeta. LXR activators could provide a new class of therapeutic agents for the treatment of cutaneous inflammatory disorders.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/22-hydroxycholesterol, http://linkedlifedata.com/resource/pubmed/chemical/25-hydroxycholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Adjuvants, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents, http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxycholesterols, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors, http://linkedlifedata.com/resource/pubmed/chemical/Oxazolone, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha, http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
246-55
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12542530-Adjuvants, Immunologic, pubmed-meshheading:12542530-Animals, pubmed-meshheading:12542530-Anti-Inflammatory Agents, pubmed-meshheading:12542530-Carcinogens, pubmed-meshheading:12542530-DNA-Binding Proteins, pubmed-meshheading:12542530-Dermatitis, Irritant, pubmed-meshheading:12542530-Disease Models, Animal, pubmed-meshheading:12542530-Epidermis, pubmed-meshheading:12542530-Female, pubmed-meshheading:12542530-Hydroxycholesterols, pubmed-meshheading:12542530-Interleukin-1, pubmed-meshheading:12542530-Male, pubmed-meshheading:12542530-Mice, pubmed-meshheading:12542530-Mice, Inbred Strains, pubmed-meshheading:12542530-Mice, Knockout, pubmed-meshheading:12542530-Orphan Nuclear Receptors, pubmed-meshheading:12542530-Oxazolone, pubmed-meshheading:12542530-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:12542530-Tetradecanoylphorbol Acetate, pubmed-meshheading:12542530-Tumor Necrosis Factor-alpha
pubmed:year
2003
pubmed:articleTitle
Liver X receptor activators display anti-inflammatory activity in irritant and allergic contact dermatitis models: liver-X-receptor-specific inhibition of inflammation and primary cytokine production.
pubmed:affiliation
Department of Dermatology, University of California, San Francisco, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't