Thalidomide increases keratinocyte proliferation and chemokine secretion in vitro

E. A. O'Toole, M. R. Nasca, P. Palicharla, D. P. West, D. T. Woodley

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We investigated the effect of thalidomide (T) on human keratinocyte (HK) proliferation as well as on metalloproteinase-9 (MMP-9) and chemokine secretion. HK viability with T was assessed by Trypan Blue exclusion. T ≤ 100 μM did not affect HK viability after 12 h. To assess the proliferate potential of HKs with T from 1 nM-100 μM, a HK thymidine incorporation assay was used. HKs were plated in 24-well trays for 2 h. T, diluted in keratinocyte medium, was added to each well and the cells were incubated for 12 h. 2 μCi of [methyl-3H] thymidine per well was added and incubation was continued for 8 h. Thymidine incorporated into DNA was extracted and counted. Control HK cultures incorporated 10,080 ± 1,100 CPM of 3-H thymidine. T at a concentration of 1 nM increased thymidine incorporation to 28,546 ± 5,604 CPM. At concentrations >1 μM there was no increase. Gelatin-zymography demonstrated no change in MMP-9 secreted into HK medium in the presence of T. To assess IL-8 secretion, HKs were incubated with T from 100 pM-100 uM for 12 h. HKs in the presence of T secreted a 2 -4-fold increase in IL-8 (range 12-21 pg/ml) compared to control HKs (range 4.5-6 pg/ml). HK proliferation is an important step in wound healing and IL-8 is known to increase HK proliferation and to be chemotactic for HKs. T may modulate HK proliferation by a chemokine-dependent pathway and therefore be of benefit in wound healing.

Original languageEnglish (US)
Number of pages1
JournalClinical Pharmacology and Therapeutics
Issue number2
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Pharmacology


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