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Aberrant production of interleukin-8 and thrombospondin-1 by psoriatic keratinocytes mediates angiogenesis.
- Source :
-
The American journal of pathology [Am J Pathol] 1994 Apr; Vol. 144 (4), pp. 820-8. - Publication Year :
- 1994
-
Abstract
- Psoriasis is a common inherited skin disease that is characterized by hyperproliferation of epidermal keratinocytes and excessive dermal angiogenesis. A growing body of evidence supports a key pathogenetic role for activated keratinocytes in the angiogenic response that accompanies psoriasis. We investigated the role of psoriatic epidermis in the aberrant expression of angiogenesis by examining the ability of pure populations of multipassaged keratinocytes obtained from the skin of normal individuals and psoriatic patients to induce angiogenesis in vivo in the rat corneal bioassay and endothelial cell chemotaxis in vitro. Media conditioned by keratinocytes from psoriatic patients, including both symptomless skin and psoriatic plaques, induced vigorous angiogenic responses in over 90% of corneas tested and potently stimulated directional migration of capillary endothelial cells in vitro. In contrast, conditioned medium from normal keratinocyte cultures was weakly positive in less than 10% of corneas assayed and failed to stimulate endothelial cell chemotaxis. Furthermore, keratinocytes from psoriatic skin exhibited a 10- to 20-fold increase in interleukin-8 production and a seven-fold reduction in thrombospondin-1 production. The angiogenic activity present in keratinocyte-conditioned media from psoriatic patients was suppressed by adding either highly purified thrombospondin-1 (125 ng) or following the addition of either normal keratinocyte-conditioned media or neutralizing interleukin-8 antibody. We conclude that psoriatic keratinocytes are phenotypically different from normal keratinocytes with respect to their angiogenic capacity and that this aberrant phenotype is attributable to a defect in the overproduction of interleukin-8 and a deficiency in the production of the angiogenesis inhibitor thrombospondin-1.
- Subjects :
- Adult
Angiogenesis Inducing Agents pharmacology
Animals
Cells, Cultured
Culture Media, Conditioned pharmacology
Endothelium, Vascular drug effects
Enzyme-Linked Immunosorbent Assay
Female
Humans
Keratinocytes cytology
Male
Middle Aged
Rats
Rats, Inbred F344
Thrombospondins
Interleukin-8 biosynthesis
Keratinocytes metabolism
Membrane Glycoproteins biosynthesis
Neovascularization, Pathologic etiology
Psoriasis metabolism
Skin blood supply
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9440
- Volume :
- 144
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 7512793