CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity

• Verfasst von: Bauer, Rüdiger von [VerfasserIn]
• Verfasst von: Oikonomou, Dimitrios [VerfasserIn]
• Verfasst von: Sulaj, Alba [VerfasserIn]
• Verfasst von: Mohammed, Sawsan [VerfasserIn]
• Verfasst von: Hotz-Wagenblatt, Agnes [VerfasserIn]
• Verfasst von: Gröne, Hermann-Josef [VerfasserIn]
• Verfasst von: Arnold, Bernd [VerfasserIn]
• Verfasst von: Falk, Christine Susanne [VerfasserIn]
• Verfasst von: Luethje, Dorit [VerfasserIn]
• Verfasst von: Erhardt, Axel [VerfasserIn]
• Verfasst von: Stern, David M. [VerfasserIn]
• Verfasst von: Bierhaus, Angelika [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Titel: CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity
• Verf.angabe: Rüdiger von Bauer, Dimitrios Oikonomou, Alba Sulaj, Sawsan Mohammed, Agnes Hotz-Wagenblatt, Hermann-Josef Gröne, Bernd Arnold, Christine Falk, Dorit Luethje, Axel Erhardt, David M. Stern, Angelika Bierhaus, and Peter P. Nawroth
• E-Jahr: 2013
• Jahr: 31 May 2013
• Umfang: 9 S.
• Fussnoten: Gesehen am 07.03.2022
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2013
• Band/Heft Quelle: 191(2013), 1, Seite 369-377
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.1201864
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1794856102

Abstract

Promiscuity of pattern recognition receptors, such as receptor for advanced glycation end products (RAGE), allows for a complex regulatory network controlling inflammation. Scavenging of RAGE ligands by soluble RAGE treatment is effective in reducing delayed-type hypersensitivity (DTH), even in RAGE−/− mice by 50% (p < 0.001). This has led to the hypothesis that molecules scavenged by soluble RAGE bind to receptors other than RAGE. This study identifies CD166/ALCAM (ALCAM) as a close structural and functional homolog of RAGE, and it shows that binding of S100B to CD166/ALCAM induces dose- and time-dependent expression of members of the NF-κB family in wild type (WT) and RAGE−/− mouse endothelial cells. Blocking CD166/ALCAM expression using small interfering RNA completely inhibited S100B-induced NF-κB activation in RAGE−/−, but not in WT cells. The in vivo significance of these observations was demonstrated by attenuation of DTH in WT and RAGE−/− animals pretreated with CD166/ALCAM small interfering RNA by 50% and 40%, respectively (p < 0.001). Experiments in ALCAM−/− animals displayed an only slight reduction of 16% in DTH, explained by compensatory reciprocal upregulation of RAGE in animals devoid of CD166/ALCAM, and vice versa. Consistently, ALCAM−/− mice, but not WT mice treated with RAGE small interfering RNA show a 35% reduction in DTH, and ALCAM−/− RAGE−/− double-knockout mice show a 27% reduction in DTH reaction. Thus, S100B is a proinflammatory cytokine bridging RAGE and CD166/ALCAM downstream effector mechanisms, both being compensatory upregulated after genetic deletion of its counterpart.