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

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...

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Hauptverfasser: Bauer, Rüdiger von (Verfasst von) , Oikonomou, Dimitrios (Verfasst von) , Sulaj, Alba (Verfasst von) , Mohammed, Sawsan (Verfasst von) , Hotz-Wagenblatt, Agnes (Verfasst von) , Gröne, Hermann-Josef (Verfasst von) , Arnold, Bernd (Verfasst von) , Falk, Christine Susanne (Verfasst von) , Luethje, Dorit (Verfasst von) , Erhardt, Axel (Verfasst von) , Stern, David M. (Verfasst von) , Bierhaus, Angelika (Verfasst von) , Nawroth, Peter Paul (Verfasst von)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 31 May 2013
In: The journal of immunology
Year: 2013, Jahrgang: 191, Heft: 1, Pages: 369-377
ISSN:1550-6606
DOI:10.4049/jimmunol.1201864
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.1201864
Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/191/1/369
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 07.03.2022
Beschreibung:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.1201864

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