Oleic acid, linoleic, EPA and DHA on the role of keratinocytes: possible topic application in the treatment of wounds

Abstract

Treatment of wounds using topical fatty acids is a common practice in the popular cultures of many countries. However, the mechanisms of action of these substances are unclear, especially regarding to the activity of fatty acids in cells involved in tissue repair, such as keratinocytes. Until recently, keratinocytes were recognized as cells involved in the process of formation of granulation tissue and reepithelialization. However, recently, they become an important player in the early stages of healing, by orchestrating the modulation of inflammatory response and migration of other cell types at wound site. When activated, keratinocytes are able to produce and secrete a wide variety of modulatores, including cytokines, growth factors and chemokines that contribute to skin inflammation and immune reactions. This study aims to determine the effects of oleic, linoleic, EPA and DHA in the healing process through focused studies in vitro and in vivo function in keratinocytes. In vivo, we will study the effects of fatty acids on keratinocytes, HaCaT lineage through the analysis of (a) DNA fragmentation, (b) membrane integrity, (c) clonogenic assay (d) release of cytokines (TNF-±, IL-1² and IL-8) and proliferation assay. If effects, trials to elucidate the signaling pathways involved in ERK1/2, Akt and MAPKp38 will be done. In vivo studies in injured and treated topically with fatty rats: (a) Macroscopic analysis of the healing process and (b) detection of pro-inflammatory cytokines (TNF-±, IL-1² and IL-8) and growth factors (KGF, VEGF and TGF-²) produced in the different phases of wound healing process. Regarding future perspectives related to this work, if there a beneficial effect is found, it might also be possible to reveal the specific mechanism involved. The potential beneficial effects of the fatty acids acids on the process of tissue repair and keratinocyte function could give rise to new opportunities for studies on signaling pathways, in addition to providing the possibility of developing further formulations (biomembranes, gels, ointments) for use in humans. (AU)