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The Osmolyte Taurine Protects against Ultraviolet B Radiation-Induced Immunosuppression¹

Nicole Rockel^*, Charlotte Esser^*, Susanne Grether-Beck^*, Ulrich Warskulat, Ulrich Flögel, Agatha Schwarz, Thomas Schwarz, Daniel Yarosh^¶, Dieter Häussinger and Jean Krutmann^2,*

^* Institut für Umweltmedizinische Forschung (IUF) an der Heinrich-Heine-Universität Düsseldorf gGmbH, Düsseldorf, Germany; Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; Department of Physiology, Heinrich-Heine-University, Düsseldorf, Germany; Clinic for Dermatology, Allergology and Venerology, Christian-Albrechts-Universität zu Kiel, Kiel, Germany; and ^¶ AGI Dermatics, Freeport, NY 11520

Organic osmolytes, such as taurine, are involved in cell volume homeostasis and cell protection. Epidermal keratinocytes possess an osmolyte strategy, i.e., they take up taurine upon hyperosmotic stress and express the corresponding transporter TAUT. UVB irradiation also triggers taurine uptake and TAUT expression in this cell type. We therefore asked whether taurine plays a role in photoprotection. By using a TAUT-deficient mouse model, lack of taurine in the skin was found to cause a significantly higher sensitivity to UVB-induced immunosuppression. This was not due to an increased generation or decreased repair of UVB-induced DNA photoproducts in the skin of these animals. Instead, decreased skin taurine levels were associated with an increased formation of the soluble immunosuppressive molecule platelet-activating factor (PAF) from the membranes of UVB-irradiated epidermal cells. Blocking PAF activity in taut-deficient mice with a PAF receptor antagonist abrogated their increased sensitivity to UVB-induced immunosuppression. Moreover, taut –/– mice were more sensitive to PAF-mediated immunosuppression than taut +/+ mice. These data suggest that taurine uptake by epidermal cells prevents undue PAF formation, and thereby photoimmunosuppression. Thus, similar to nucleotide excision repair, taurine uptake is critically involved in photoprotection of the skin.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported through the Deutsche Forschungsgemeinschaft (SFB 503 "Molecular and cellular mediators of exogenous noxes" and SFB 575 "Experimental Hepatology"), the Bundesministerium für Umwelt, and the BMFZ at the Heinrich-Heine University of Düsseldorf.

² Address correspondence and reprint requests to Prof. Dr. Jean Krutmann, Institut für Umweltmedizinische Forschung (IUF) gGmbH, Auf’m Hennekamp 50, Düsseldorf, Germany. E-mail address: krutmann{at}rz.uni-duesseldorf.de

³ Abbreviations used in this paper: PAF, platelet-activating factor; ¹H NMR spectroscopy, proton nuclear magnetic resonance spectroscopy; CHS, contact hypersensitivity; CPD, cyclobutyl pyrimidine dimers; DNFB, dinitrofluorobenzene; MEC, primary murine epidermal cells; AMD, automated multiple development; RPS, ribosomal protein subunit.