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

Rüdiger Von Bauer, Dimitrios Oikonomou, Alba Sulaj, Sawsan Mohammed, Agnes Hotz-Wagenblatt, Hermann Josef Gröne, Bernd Arnold, Christine Falk, Dorit Luethje, Axel Erhardt, David Stern, Angelika Bierhaus, Peter P. Nawroth

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)369-377
Number of pages9
JournalJournal of Immunology
Volume191
Issue number1
DOIs
StatePublished - Jul 1 2013

Fingerprint

Activated-Leukocyte Cell Adhesion Molecule
Delayed Hypersensitivity
Small Interfering RNA
Advanced Glycosylation End Product-Specific Receptor
Pattern Recognition Receptors
Cytokine Receptors

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Von Bauer, R., Oikonomou, D., Sulaj, A., Mohammed, S., Hotz-Wagenblatt, A., Gröne, H. J., ... Nawroth, P. P. (2013). CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity. Journal of Immunology, 191(1), 369-377. https://doi.org/10.4049/jimmunol.1201864

CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity. / Von Bauer, Rüdiger; Oikonomou, Dimitrios; Sulaj, Alba; Mohammed, Sawsan; Hotz-Wagenblatt, Agnes; Gröne, Hermann Josef; Arnold, Bernd; Falk, Christine; Luethje, Dorit; Erhardt, Axel; Stern, David; Bierhaus, Angelika; Nawroth, Peter P.

In: Journal of Immunology, Vol. 191, No. 1, 01.07.2013, p. 369-377.

Research output: Contribution to journalArticle

Von Bauer, R, Oikonomou, D, Sulaj, A, Mohammed, S, Hotz-Wagenblatt, A, Gröne, HJ, Arnold, B, Falk, C, Luethje, D, Erhardt, A, Stern, D, Bierhaus, A & Nawroth, PP 2013, 'CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity', Journal of Immunology, vol. 191, no. 1, pp. 369-377. https://doi.org/10.4049/jimmunol.1201864
Von Bauer R, Oikonomou D, Sulaj A, Mohammed S, Hotz-Wagenblatt A, Gröne HJ et al. CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity. Journal of Immunology. 2013 Jul 1;191(1):369-377. https://doi.org/10.4049/jimmunol.1201864
Von Bauer, Rüdiger ; Oikonomou, Dimitrios ; Sulaj, Alba ; Mohammed, Sawsan ; Hotz-Wagenblatt, Agnes ; Gröne, Hermann Josef ; Arnold, Bernd ; Falk, Christine ; Luethje, Dorit ; Erhardt, Axel ; Stern, David ; Bierhaus, Angelika ; Nawroth, Peter P. / CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity. In: Journal of Immunology. 2013 ; Vol. 191, No. 1. pp. 369-377.
@article{e1d2c5cee5594a78abb9437f3a3ff796,
title = "CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity",
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.",
author = "{Von Bauer}, R{\"u}diger and Dimitrios Oikonomou and Alba Sulaj and Sawsan Mohammed and Agnes Hotz-Wagenblatt and Gr{\"o}ne, {Hermann Josef} and Bernd Arnold and Christine Falk and Dorit Luethje and Axel Erhardt and David Stern and Angelika Bierhaus and Nawroth, {Peter P.}",
year = "2013",
month = "7",
day = "1",
doi = "10.4049/jimmunol.1201864",
language = "English (US)",
volume = "191",
pages = "369--377",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

TY - JOUR

T1 - CD166/ALCAM mediates proinflammatory effects of S100B in delayed type hypersensitivity

AU - Von Bauer, Rüdiger

AU - Oikonomou, Dimitrios

AU - Sulaj, Alba

AU - Mohammed, Sawsan

AU - Hotz-Wagenblatt, Agnes

AU - Gröne, Hermann Josef

AU - Arnold, Bernd

AU - Falk, Christine

AU - Luethje, Dorit

AU - Erhardt, Axel

AU - Stern, David

AU - Bierhaus, Angelika

AU - Nawroth, Peter P.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84879616614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879616614&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1201864

DO - 10.4049/jimmunol.1201864

M3 - Article

VL - 191

SP - 369

EP - 377

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -