Prospective phospholipid markers for skin sensitization prediction in keratinocytes: A phospholipidomic approach

Prevalence of skin inflammatory disorders has increased in recent years being estimated that 15–20% of the general population suffers from allergic contact dermatitis (ACD). Currently, the sensitizing potential of chemicals is assessed through animal tests; however growing ethical concerns and actual legislative framework impose the development of new alternative tests. Several genomic and proteomic approaches have already indicated some potential biomarkers, but lipidomic analysis was not so far explored with this purpose. A growing body of data suggests that phospholipids (PLs) play important roles in the modulation of immune responses. Therefore, this work focused in identifying changes in the PLs profile of human keratinocytes (KCs). For that, HaCaT cell line was exposed to two immune stimulators: the strong skin allergen 2,4-dinitrofluorobenzene (DNFB) and the non-allergenic stimulus LPS, and to the irritant benzalkonium chloride (BC), using off line TLC–ESI-MS, HPLC-MS and MS/MS. LPS and DNFB reduced PS class relative content, corroborating with consistent changes observed in its molecular profile. PC profile was also altered by immune stimulators. These findings suggest that PC and PS molecular species may discriminate immunogenic compounds from irritants. Analysis of such alterations may be therefore valuable in a future in vitro test platform for skin sensitization prediction.

► There is a need of in vitro tests to evaluate skin sensitizing potential of chemicals.
► Phospholipid changes in keratinocytes induced by allergen and irritant was evaluated.
► Skin allergens induced significant changes in phosphatadylserine content and profile.
► Skin irritant changed phosphatidylethanolamine and phosphatidylcholine profiles.
► Phospholipid biomarkers could be useful to predict skin sensitization.