Expression of human solute carrier family transporters in skin: possible contributor to drug-induced skin disorders

Solute carrier (SLC) transporters play important roles in absorption and disposition of drugs in cells; however, the expression pattern of human SLC transporters in the skin has not been determined. In the present study, the expression patterns of 28 human SLC transporters were determined in the human skin. Most of the SLC transporter family members were either highly or moderately expressed in the liver, while their expression was limited in the skin and small intestine. Treatment of human keratinocytes with a reactive metabolite of ibuprofen significantly reduced cell viability. Expression array analysis revealed that S100 calcium binding protein A7A (S100A7A) was induced nearly 50-fold in dermal cells treated with ibuprofen acyl-glucuronide. Determination of the expression of drug-metabolizing enzymes as well as drug transporters prior to the administration of drugs would make it possible to avoid the development of idiosyncratic skin diseases in individuals.

[1]  N. Fusenig,et al.  Epidermal organization and differentiation of HaCaT keratinocytes in organotypic coculture with human dermal fibroblasts. , 1999, The Journal of investigative dermatology.

[2]  C. Haudenschild,et al.  Early Interactions Between Blood Cells and Severely Damaged Rabbit Aorta , 1971, European journal of clinical investigation.

[3]  T. Ruzicka,et al.  Vitamin D analog calcipotriol suppresses the Th17 cytokine-induced proinflammatory S100 "alarmins" psoriasin (S100A7) and koebnerisin (S100A15) in psoriasis. , 2012, The Journal of investigative dermatology.

[4]  A. Ungell,et al.  Variability in mRNA expression of ABC- and SLC-transporters in human intestinal cells: comparison between human segments and Caco-2 cells. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[5]  J. Lipozenčić,et al.  Drug induced psoriasis. , 2011, Acta dermatovenerologica Croatica : ADC.

[6]  A. Rzhetsky,et al.  The human ATP-binding cassette (ABC) transporter superfamily. , 2001, Genome research.

[7]  R. Kim,et al.  Organic anion‐transporting polypeptide (OATP) transporter family and drug disposition , 2003, European journal of clinical investigation.

[8]  P. Watson,et al.  Psoriasin (S100A7). , 1998, The international journal of biochemistry & cell biology.

[9]  Ryoichi Fujiwara,et al.  Toxicological Evaluation of Acyl Glucuronides of Nonsteroidal Anti-Inflammatory Drugs Using Human Embryonic Kidney 293 Cells Stably Expressing Human UDP-Glucuronosyltransferase and Human Hepatocytes , 2011, Drug Metabolism and Disposition.

[10]  A. Sidoroff,et al.  Drug-Induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis , 2000, American journal of clinical dermatology.

[11]  A. Kaplan,et al.  Drug-induced skin disease. , 1984, The Journal of allergy and clinical immunology.

[12]  C. King,et al.  Glucuronidation of carboxylic acid containing compounds by UDP-glucuronosyltransferase isoforms. , 2004, Archives of biochemistry and biophysics.

[13]  J. J. Gayford,et al.  The Side-Effects of Carbamazepine , 1969, Proceedings of the Royal Society of Medicine.

[14]  Shengjie Li,et al.  Recent Advances , 2018, Journal of Optimization Theory and Applications.

[15]  N. Tsankov,et al.  Drug-induced psoriasis. Recognition and management. , 2000, American journal of clinical dermatology.

[16]  R. Fujiwara,et al.  Expression pattern of human ATP-binding cassette transporters in skin , 2013, Pharmacology research & perspectives.

[17]  Kei-ichi Minami,et al.  An in vitro drug-induced hepatotoxicity screening system using CYP3A4-expressing and gamma-glutamylcysteine synthetase knockdown cells. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[18]  M. Akabas,et al.  Identification of an Intestinal Folate Transporter and the Molecular Basis for Hereditary Folate Malabsorption , 2006, Cell.

[19]  R. Kim,et al.  Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. , 2006, Gastroenterology.

[20]  R. M. Robinson,et al.  Stevens-Johnson syndrome plus toxic hepatitis due to ibuprofen. , 1978, New York state journal of medicine.

[21]  Charles Elkan,et al.  The Transporter Classification Database: recent advances , 2008, Nucleic Acids Res..

[22]  N. Tsankov,et al.  Drug-Induced Psoriasis , 2000 .

[23]  J. Roujeau,et al.  Drug-induced toxic epidermal necrolysis (Lyell syndrome) in patients infected with the human immunodeficiency virus. , 1992, Journal of the American Academy of Dermatology.

[24]  K. Inui,et al.  Gene expression and regulation of drug transporters in the intestine and kidney. , 2007, Biochemical pharmacology.

[25]  R. Tukey,et al.  Glucuronidation of drugs in humanized UDP-glucuronosyltransferase 1 mice: Similarity with glucuronidation in human liver microsomes , 2013, Pharmacology research & perspectives.

[26]  C. Funk.  The role of hepatic transporters in drug elimination. , 2008, Expert opinion on drug metabolism & toxicology.

[27]  C. Enerbäck,et al.  Expression patterns of S100A7 (psoriasin) and S100A9 (calgranulin‐B) in keratinocyte differentiation , 2005, Experimental dermatology.

[28]  Xiao-dong Liu,et al.  Transport of carbamazepine and drug interactions at blood-brain barrier , 2006, Acta Pharmacologica Sinica.

[29]  F. Sirotnak,et al.  Carrier-mediated membrane transport of folates in mammalian cells. , 1999, Annual review of nutrition.

[30]  Katsuhisa Inoue,et al.  Molecular and functional characteristics of proton-coupled folate transporter. , 2009, Journal of pharmaceutical sciences.

[31]  R. Tukey,et al.  Importance of UDP-Glucuronosyltransferase 1A1 Expression in Skin and Its Induction by UVB in Neonatal Hyperbilirubinemia , 2013, Molecular Pharmacology.

[32]  J. Craig,et al.  Stevens-Johnson syndrome associated with methotrexate treatment for non-Hodgkin's lymphoma. , 1993, Ulster medical journal.

[33]  T. Shiohara,et al.  Drug-induced Hypersensitivity Syndrome(DIHS): A Reaction Induced by a Complex Interplay among Herpesviruses and Antiviral and Antidrug Immune Responses. , 2006, Allergology international : official journal of the Japanese Society of Allergology.

[34]  L. Harber,et al.  Pathogenic mechanisms of drug-induced photosensitivity. , 1972, The Journal of investigative dermatology.

[35]  F. Russel,et al.  Mechanisms of renal anionic drug transport. , 2008, European journal of pharmacology.

[36]  R. Kim,et al.  Transporters and drug therapy: Implications for drug disposition and disease , 2005, Clinical pharmacology and therapeutics.

[37]  A. Fujimura,et al.  Evaluation of the interaction between nonsteroidal anti-inflammatory drugs and methotrexate using human organic anion transporter 3-transfected cells. , 2008, European journal of pharmacology.

[38]  H. Hosomi,et al.  CYP2C9-Mediated Metabolic Activation of Losartan Detected by a Highly Sensitive Cell-Based Screening Assay , 2011, Drug Metabolism and Disposition.

[39]  Per Artursson,et al.  Expression of Thirty-six Drug Transporter Genes in Human Intestine, Liver, Kidney, and Organotypic Cell Lines , 2007, Drug Metabolism and Disposition.

[40]  E. van de Steeg,et al.  Methotrexate Pharmacokinetics in Transgenic Mice with Liver-Specific Expression of Human Organic Anion-Transporting Polypeptide 1B1 (SLCO1B1) , 2009, Drug Metabolism and Disposition.