Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-10
pubmed:abstractText
Aminopeptidase inhibitors strongly affect proliferation, differentiation, and function of immune cells and show therapeutic potential in inflammatory disorders. In psoriatic lesions, keratinocytes display increased cellular turnover and disturbed differentiation, leading to epidermal hyperplasia accompanied by the loss of stratum granulosum. Here, we report in the HaCaT hyperproliferative keratinocyte cell line as well as in two primary keratinocyte strains in vitro a molecular and biochemical analysis of the expression of both membrane and cytosol alanyl aminopeptidase (cAAP) on the mRNA, protein, and enzymatic activity level. We found a clear dose-dependent suppression of DNA synthesis in vitro in the presence of the inhibitors actinonin, bestatin, and the cAAP-specific inhibitor PAC-22 correlating well with the simultaneous decrease in enzyme activity. In vivo, actinonin dose-dependently restored the stratum granulosum and ameliorated the impaired keratinocyte differentiation in the mouse tail model of psoriasis. Taken together, these data suggest that targeting alanyl aminopeptidases may be beneficial for psoriasis and other inflammatory skin disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-291X
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
321
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
795-801
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15358097-Animals, pubmed-meshheading:15358097-Antigens, CD13, pubmed-meshheading:15358097-Base Sequence, pubmed-meshheading:15358097-Cell Differentiation, pubmed-meshheading:15358097-Cell Division, pubmed-meshheading:15358097-Cell Line, pubmed-meshheading:15358097-Cell Membrane, pubmed-meshheading:15358097-Cells, Cultured, pubmed-meshheading:15358097-Cytosol, pubmed-meshheading:15358097-DNA, pubmed-meshheading:15358097-Enzyme Inhibitors, pubmed-meshheading:15358097-Gene Expression, pubmed-meshheading:15358097-Humans, pubmed-meshheading:15358097-Hydroxamic Acids, pubmed-meshheading:15358097-Keratinocytes, pubmed-meshheading:15358097-Leucine, pubmed-meshheading:15358097-Male, pubmed-meshheading:15358097-Mice, pubmed-meshheading:15358097-Psoriasis, pubmed-meshheading:15358097-RNA, Messenger
pubmed:year
2004
pubmed:articleTitle
Identification of extra- and intracellular alanyl aminopeptidases as new targets to modulate keratinocyte growth and differentiation.
pubmed:affiliation
Department of Dermatology and Venereology, IMTM, Leipziger Str. 44, 39120 Magdeburg, Germany. Anja.Thielitz@medizin.uni-magdeburg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't