TY - JOUR
T1 - Thalidomide increases human keratinocyte migration and proliferation
AU - Nasca, Maria R.
AU - O'Toole, Edel A.
AU - Palicharla, Prema
AU - West, Dennis P.
AU - Woodley, David T.
N1 - Funding Information:
This study was supported by Northwestern Memorial Foundation (DPW), a Howard Hughes Medical Institute Physician Fellowship (EOT), and Grants P01 AR41045, R01 AR46538, and R01 AR33625 from the National Institute of Health, Bethesda, MD (DTW). Maria R. Nasca carried out this work as a visiting Assistant Professor at North-western University.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behcet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 μM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2.5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.
AB - Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behcet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 μM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2.5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.
KW - Cytokine
KW - Re-epithelialization
KW - Wound healing
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U2 - 10.1046/j.1523-1747.1999.00744.x
DO - 10.1046/j.1523-1747.1999.00744.x
M3 - Article
C2 - 10571725
AN - SCOPUS:0032735236
VL - 113
SP - 720
EP - 724
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -