title: The effects of caffeine on wound healing.
abstract: The purine alkaloid caffeine is a major component of many beverages such as coffee and tea. Caffeine and its metabolites theobromine and xanthine have been shown to have antioxidant properties. Caffeine can also act as adenosine-receptor antagonist. Although it has been shown that adenosine and antioxidants promote wound healing, the effect of caffeine on wound healing is currently unknown. To investigate the effects of caffeine on processes involved in epithelialisation, we used primary human keratinocytes, HaCaT cell line and ex vivo model of human skin. First, we tested the effects of caffeine on cell proliferation, differentiation, adhesion and migration, processes essential for normal wound epithelialisation and closure. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) proliferation assay to test the effects of seven different caffeine doses ranging from 0·1 to 5 mM. We found that caffeine restricted cell proliferation of keratinocytes in a dose-dependent manner. Furthermore, scratch wound assays performed on keratinocyte monolayers indicated dose-dependent delays in cell migration. Interestingly, adhesion and differentiation remained unaffected in monolayer cultures treated with various doses of caffeine. Using a human ex vivo wound healing model, we tested topical application of caffeine and found that it impedes epithelialisation, confirming in vitro data. We conclude that caffeine, which is known to have antioxidant properties, impedes keratinocyte proliferation and migration, suggesting that it may have an inhibitory effect on wound healing and epithelialisation. Therefore, our findings are more in support of a role for caffeine as adenosine-receptor antagonist that would negate the effect of adenosine in promoting wound healing.
authors.affiliation: Faculty of Medical Sciences, The University of the West Indies, St. Michael, Barbados. nkemcho.ojeh@cavehill.uwi.edu.
authors.forename: Nkemcho
authors.initials: N
authors.lastname: Ojeh
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Olivera
authors.initials: O
authors.lastname: Stojadinovic
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Irena
authors.initials: I
authors.lastname: Pastar
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sawaya
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Yin
authors.affiliation: Wound Healing and Regenerative Medicine Research Program, Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, FL, USA.
authors.forename: Marjana
authors.initials: M
authors.lastname: Tomic-Canic
mesh_terms: D002110:Caffeine; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D015603:Keratinocytes; D013778:Tetrazolium Salts; D013844:Thiazoles; D014945:Wound Healing
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D002110:Caffeine; C022616:thiazolyl blue
keywords: Caffeine; Ex vivo model; Migration; Proliferation; Re-epithelialisation; Wound healing