PMID- 24995813
OWN - NLM
STAT- MEDLINE
DCOM- 20141031
LR  - 20171116
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 463
IP  - 1
DP  - 2014 Oct 1
TI  - cAMP ameliorates inflammation by modulation of macrophage receptor for advanced 
      glycation end-products.
PG  - 75-82
LID - 10.1042/BJ20140084 [doi]
AB  - Clarification of the roles of PAMPs (pathogen-associated molecular patterns) and 
      DAMPs (damage-associated molecular patterns) is indispensable for therapeutic 
      strategies against various inflammatory diseases. RAGE (receptor for advanced 
      glycation end-products) is one of the PRRs (pattern recognition receptors) and 
      has been implicated in autoimmune and inflammatory diseases. Effective remedies 
      targeting RAGE are required for the diseases. In the present study, we show that 
      cAMP-induced modulation of the RAGE isoform in macrophages can control the 
      inflammatory state in both in vitro and in vivo experimental conditions. The RAGE 
      ligand S100B stimulated MCP-1 (monocyte chemoattractant protein-1) secretion from 
      peritoneal macrophages, but cAMP elevation suppressed it by converting the RAGE 
      isoform from a membrane-bound into a soluble form. This shedding is the result of 
      ectodomain cleavage of mRAGE (membrane-bound RAGE) by MMP9 (matrix 
      metalloproteinase 9). Furthermore, forskolin significantly inhibited peritoneal 
      macrophage accumulation in a mouse S100B-induced peritonitis model. These results 
      suggest that cAMP serves as a negative regulator of ligand-RAGE signalling and 
      macrophage recruitment by mRAGE down-regulation and formation of decoys as 
      soluble receptors. The present study should deepen our understanding of the 
      pathogenesis of RAGE-mediated tissue derangement and provide new clues for 
      overcoming RAGE-related inflammatory diseases.
FAU - Motoyoshi, So
AU  - Motoyoshi S
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Yamamoto, Yasuhiko
AU  - Yamamoto Y
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Munesue, Seiichi
AU  - Munesue S
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Igawa, Hirobumi
AU  - Igawa H
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Harashima, Ai
AU  - Harashima A
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Saito, Hidehito
AU  - Saito H
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Han, Dong
AU  - Han D
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Watanabe, Takuo
AU  - Watanabe T
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
FAU - Sato, Hiroshi
AU  - Sato H
AD  - daggerDepartment of Molecular Virology and Oncology, Cancer Research Institute, 
      Kanazawa University, Kanazawa, 920-1192, Japan.
FAU - Yamamoto, Hiroshi
AU  - Yamamoto H
AD  - *Department of Biochemistry and Molecular Vascular Biology, Kanazawa University 
      Graduate School of Medical Sciences, Kanazawa, 920-8640, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (S100 Calcium Binding Protein beta Subunit)
RN  - 0 (S100b protein, mouse)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 3.4.24.35 (Mmp9 protein, mouse)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics/metabolism
MH  - Cyclic AMP/genetics/*metabolism
MH  - Inflammation/genetics/metabolism/pathology
MH  - Macrophages, Peritoneal/*metabolism/pathology
MH  - Matrix Metalloproteinase 9/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Protein Structure, Tertiary
MH  - Proteolysis
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/genetics/*metabolism
MH  - S100 Calcium Binding Protein beta Subunit/genetics/metabolism
MH  - *Signal Transduction
EDAT- 2014/07/06 06:00
MHDA- 2014/11/02 06:00
CRDT- 2014/07/05 06:00
PHST- 2014/07/05 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2014/11/02 06:00 [medline]
AID - BJ20140084 [pii]
AID - 10.1042/BJ20140084 [doi]
PST - ppublish
SO  - Biochem J. 2014 Oct 1;463(1):75-82. doi: 10.1042/BJ20140084.