Analysis of human in vivo irritated epidermis: differential profiles induced by sodium lauryl sulphate and nonanoic acid

Irritant contact dermatitis (ICD) pathogenesis is not completely understood and the genes participating in the epidermal response towards chemical irritants are only partly known. It is commonly accepted that different irritants have different mechanisms of action in the development of ICD. To define the differential molecular events induced in the epidermis by different irritants, we collected sequential biopsies (½, 4 and 24 hours after a single exposure and at day 11 after repeated exposure) from human volunteers exposed to sodium lauryl sulphate (SLS) or nonanoic acid (NON). Gene expression analysis using high-density oligonucleotide microarrays revealed essentially different pathway responses ½ h after exposure: NON transiently induced the IL-6 pathway as well as a number of mitogen activated signalling cascades including ERK and growth factor receptor signalling, whereas SLS transiently downregulated cellular energy metabolism pathways. Differential expression of the cyclooxygenase-2 and matrix metalloproteinase 3 transcripts was confirmed immunohistochemically. After cumulative exposure, 883 genes were differentially expressed while 26 suggested common biomarkers were identified . In conclusion, we bring new insights into two hitherto less well elucidated phases of skin irritancy: the very initial as well as the late phase after single and cumulative exposure, respectively. 36 healthy volunteers were exposed to the skin irritants SLS (n=18) or NON (n=18). Samples from 18 volunteers (9 SLS and 9 NON-exposed) were selected for the microarray experiment. Samples were obtained according to elapsed time following a single cutaneous exposure: 0.5 h, 4h and 24h. Moreover, samples were obtained at day 11 coresponding to a cumulatively (10 min for 5+4 days) irritated skin site. A balanced incomplete block design was used to obtain samples from the 4 time points; however, 0h samples (controls) were obtained for all subjects. Samples from the time point 0.5 h were of special interest and therefore doubled. Thus, 24 chips were hybridized for each irritant giving a total of 48 chips in the experiment. The relative contribution of chips per timepoint for each irritant: 0h (n=9), 0.5h (n=6), 4h (n=3), 24h (n=3), day 11 (n=3).