Thalidomide increases human keratinocyte migration and proliferation

Thalidomide is reported to have therapeutic utility in the treatment of pyo derma gangrenosum, Behcet's disease, aphthous ulcers, and skin wounds. We i nvestigated the effect of thalidomide on human keratinocyte proliferation a nd migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 mu M did not affect keratinocyte viability. Using a thymidine incorporation assay, we found tha t thalidomide, at therapeutic concentrations, induced more than a 2.5-fold increase in the proliferative potential of the cells. Keratinocyte migratio n was assessed by two independent motility assays: a colloidal gold assay a nd an in vitro scratch assay. At optimal concentrations, thalidomide increa sed keratinocyte migration on a collagen matrix more than 2-fold in the col loidal gold assay and more than 3-fold in the scratch assay over control. A lthough pro-migratory, thalidomide did not alter the level of metalloprotei nase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4 -fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellu lar autocrine factor. Human keratinocyte migration and proliferation are es sential for re-epithelialization of skin wounds. Interleukin-8 increases hu man keratinocyte migration and proliferation and is chemotactic for keratin ocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.