Abnormal Expression Of MAPK And Keratinocyte Differentiation Markers In Skin Lesions From Dioxin-exposed Humans With Chloracne

Objective:Dioxins are a class of polychlorinated aromatic hydrocarbons of persistent environmental toxicity which are formed as an unwanted by-product in the manufacture of chlorinated hydrocarbons,burning of offal,et al.Dioxins can elicit wide spectrum of toxic responses in humans including reproductive,developmental and immunologic toxicities as well as potential carcinogenicity.It is the only skin effects of dioxin exposure,especially chloracne,which is regarded as a reliable indicator of heavy dioxin exposure.In the present study,we measured the expression of phosphorylated EGFR protein and phosphorylated MAPK protein,CK17 and TGk mRNA,and CK17 and TGk protein in all chloracne tissues and normal skin.The goal was to clarify the effects of p-EGFR,p-MAPK,CK17,TGk,CK17 and TGk on dioxin induced chloracne and to provide some sound proof for the further research in molecular mechanisms of chloracne.Methods:The disease group comes from man workers who suffer from chloracne due to the process with pentachlorophenol sodium(Na-PCP)in a chemical plant in Tianjin.Control group is chosen from normal people in Tianjin,who don't have such kind of vocational history and contact history.The two groups have excellent comparability in demography feature.To obey the "minimum wound" principle,the skin samples were taken from both the disease group and the control group.Every piece of skin is 0.5×0.2 of diameter×depth and washed quickly in sodium chloride after ex vivo,then preserved in liquid nitrogen.Immunofluorescence was used for the measurement of the expression for phosphorylated EGFR and phosphorylated MAPK protein of human epidermis,mRNA fluorescence in situ hybridization and Confocal Laser Scanning Microscope used for the measurement of the expression of CK17 and TGk,immunohistochemistry was used for the measurement of CK17 and TGk protein.Results:Firstly,in this study,we investigated 12 people of chloracne as disease group,the average age is(52.08±7.62)year old;12 people in control group is formed by the average age of(51.42±5.30)year old.The two groups have excellent comparability in age,body mass index(BMI),the percentage of smoking and drinking(P＞0.05).Secondly,p-EGFR and p-MAPK was found in all chloracne tissues,whereas no expression of phosphorylated EGFR protein and phosphorylated MAPK protein was found in control group.In the skin of chloracne patient,p-EGFR was mainly distributed in the membrane and the cytoplasm,especially in the vicinity of membrane;major positive signal of p-MAPK is in core and cytoplasm.Thirdly, CK17 and CK17 were found in all chloracne tissues,whereas no expression was found in control group.In the skin of chloracne patient,the positive signals were found mainly in the stratum spinosum.The positive expression of TGk and TGk could be found in tissues of normal skin,the positive signals were found mainly in the stratum granulosum.In the chloracne tissues,the positive signals were found more significantly in the stratum granulosum and stratum spinosum.Conclusion:There is an abnormal activation of EFGR and MAPK in the skin of chloracne patient.Hyperproliferation of chloracne keratinocytes may be closely correlated with higher activity of EGFR and MAPK in chloracne lesions.Abnormal expression of CK17 and TGk in gene and protein level may disturb normal proliferation and differentiation of human epidermis cell,and lead to the form and persistence of chlroacne.