Hanan Osman-Ponchet
Skin is the largest organ in the human body and is one of the major targets of air pollution. There is increasing evidence indicating that ATP-binding cassette (ABC) family transporters play an important role in the transdermal absorption of their substrates [1-4]. Exposure of the skin to air pollutants has been associated with inflammation with increasing production of pro-inflammatory cytokines. The connection between inflammation and ABC transporters transcript levels in the skin is not known. This study investigated the effect of inflammation on the expression levels of ABC transporters in normal human keratinocytes (NHK). NHK (Sterlab France) were treated with pro-inflammatory mediator lipopolysaccharide (LPS). mRNA expression of TNF-alpha, CXCL8 (IL-8), ABCB1, ABCC1, ABCC2 and ABCG2 was measured by quantitative real time RT-PCR. Treatment with LPS up-regulated the mRNA expression of TNF-alpha and IL-8, confirming the inflammatory properties of LPS in human keratinocytes. While LPS treatment had no effect on the expression of ABCG2, it increased the expression of ABCC1 and ABCC2 in human keratinocytes. This study clearly shows a connection between inflammation and ABC transporters transcript levels in human keratinocytes. This finding is of great importance and need to be considered in pharmacokinetic evaluation of anti-inflammatory agentswhentreatinginflammatoryskin..
Speaker Publications:
1.Osman-Ponchet et al., Characterization of ABC transporters in human skin. Drug Metabol. Drug Interact., 29 (2014), pp. 91-100
2.Osman-Ponchet et al., Expression of drug transporters in the human skin: comparison in different species and models and its implication for drug development. ADMET DMPK, 5 (2017), pp. 75-84
3.Alriquet et al., Characterization of SLC transporters in human skin. ADMET DMPK, 3 (2015), pp. 34-44
4.Clerbaux et al., Membrane transporter data to support kinetically-informed chemical risk assessment using non-animal methods: Scientific and regulatory perspectives. Environment International, 26 (2019), pp. 659-671
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