Cigarette smoke affects SRB1 levels in human keratynocites via H202 production

The pathological effects of cigarette smoke (CS) have been extensively documented and many diseases such as emphysema and lung cancer are directly linked to the consequences of chronic smoke exposure. The combustion of CS produces over 4,000 different compounds in gaseous and particulate states that are able to induce oxidative stress to the cells exposed to the tobacco smoke. In addition, side stream smoke has been shown to be nearly as toxic as direct stream, therefore CS present two-fold heath problem to both passive and active smokers. Skin acts as a first line of defense against environmental trauma. The upper layer of the skin, the stratum corneum (SC), is composed by lipid barrier that contains unsaturated lipids that are susceptible to oxidation. The alteration of the skin lipids composition by the exposure to environmental stressors such as CS can affect the capacity of the SC to protect us from dehydration and external dangers. Scavenger Receptor B1 (SR-B1), one of the large family of scavenger receptors, has been shown to be involved in the uptake of cholesterol from HDL to peripheral tissues via apo A-1 mediated processes and also to be important in the delivery of tocopherol to the cells, therefore its role in skin homeostasis is crucial. In the present studies the effects of CS and of products related to CS such as acrolein, 4HNE and H2O2 on SR-B1 expression in human keratinocytes were assessed. CS exposure induced a significant decrease of SR-B1 expression and the formation of acrolein and 4NHE protein adducts. On the other hand, cells treated with several doses of acrolein or 4HNE or H2O2 did not affect SR-B1 levels. The treatment with glucose oxidase induces the same effect of CS as to concern SR-B1 levels and this was reversed when cells were treated with catalase. In addition, CS induced the activation of NADPH oxidase measured as p67 translocation from the cytoplasm to the membrane. The data from this study show that CS decreases the levels of SR-B1 in human keratinocytes and this effect is mainly driven by the production of H2O2 (exogenous and endogenous). The decrease of SR-B1 could lead to the disturbance of the skin lipid barrier affecting skin physiology and be a possible cause to skin disorders such as skin aging and wound healing linked to CS exposure.