Abstract
Objective. The accumulation of advanced glycation end products (AGEs), S100A12, and high mobility group box chromosomal protein 1 has been associated with joint inflammation in rheumatoid arthritis (RA). This study was undertaken to determine the induction of the receptor for these proteins, termed receptor for AGEs (RAGE), in synovial tissue (ST) macrophages from RA patients. Methods. RAGE and CD68 expression in ST were determined by 2-color immunofluorescence labeling. Cell surface and messenger RNA (mRNA) expression of RAGE were examined by flow cytometry and reverse transcriptase-polymerase chain reaction (PCR) or real-time PCR, respectively. Results. CD68+ lining macrophages, like the vasculature, expressed high levels of RAGE in inflamed ST from RA patients. RAGE mRNA expression was significantly higher in RA ST than in ST from patients with osteoarthritis. RAGE mRNA levels were significantly higher in ST macrophages and normal endothelial cells than in ST CD4+ T cells and synovial fibroblasts stimulated with tumor necrosis factor α and interleukin-l (IL-1β). Cell surface RAGE was highly induced on normal monocytes after a 24-hour incubation with a 20% concentration of RA ST cell culture supernatants. RAGE mRNA expression in adherent monocytes was augmented by various cytokines, most potently by IL-1β. Conclusion. These results indicate that RAGE overexpression in lining macrophages may be induced, at least in part, by cytokines such as IL-1, leading to the amplification of inflammatory responses mediated by RAGE ligands that are abundant in RA joints.
| Original language | English |
|---|---|
| Pages (from-to) | 97-104 |
| Number of pages | 8 |
| Journal | Arthritis and Rheumatism |
| Volume | 54 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 2006 |
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ASJC Scopus subject areas
- Immunology
- Rheumatology
Cite this
Increased expression of receptor for advanced glycation end products by synovial tissue macrophages in rheumatoid arthritis. / Sunahori, Katsue; Yamamura, Masahiro; Yamana, Jiro; Takasugi, Koji; Kawashima, Masanori; Makino, Hirofumi.
In: Arthritis and Rheumatism, Vol. 54, No. 1, 01.01.2006, p. 97-104.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Increased expression of receptor for advanced glycation end products by synovial tissue macrophages in rheumatoid arthritis
AU - Sunahori, Katsue
AU - Yamamura, Masahiro
AU - Yamana, Jiro
AU - Takasugi, Koji
AU - Kawashima, Masanori
AU - Makino, Hirofumi
PY - 2006/1/1
Y1 - 2006/1/1
N2 - Objective. The accumulation of advanced glycation end products (AGEs), S100A12, and high mobility group box chromosomal protein 1 has been associated with joint inflammation in rheumatoid arthritis (RA). This study was undertaken to determine the induction of the receptor for these proteins, termed receptor for AGEs (RAGE), in synovial tissue (ST) macrophages from RA patients. Methods. RAGE and CD68 expression in ST were determined by 2-color immunofluorescence labeling. Cell surface and messenger RNA (mRNA) expression of RAGE were examined by flow cytometry and reverse transcriptase-polymerase chain reaction (PCR) or real-time PCR, respectively. Results. CD68+ lining macrophages, like the vasculature, expressed high levels of RAGE in inflamed ST from RA patients. RAGE mRNA expression was significantly higher in RA ST than in ST from patients with osteoarthritis. RAGE mRNA levels were significantly higher in ST macrophages and normal endothelial cells than in ST CD4+ T cells and synovial fibroblasts stimulated with tumor necrosis factor α and interleukin-l (IL-1β). Cell surface RAGE was highly induced on normal monocytes after a 24-hour incubation with a 20% concentration of RA ST cell culture supernatants. RAGE mRNA expression in adherent monocytes was augmented by various cytokines, most potently by IL-1β. Conclusion. These results indicate that RAGE overexpression in lining macrophages may be induced, at least in part, by cytokines such as IL-1, leading to the amplification of inflammatory responses mediated by RAGE ligands that are abundant in RA joints.
AB - Objective. The accumulation of advanced glycation end products (AGEs), S100A12, and high mobility group box chromosomal protein 1 has been associated with joint inflammation in rheumatoid arthritis (RA). This study was undertaken to determine the induction of the receptor for these proteins, termed receptor for AGEs (RAGE), in synovial tissue (ST) macrophages from RA patients. Methods. RAGE and CD68 expression in ST were determined by 2-color immunofluorescence labeling. Cell surface and messenger RNA (mRNA) expression of RAGE were examined by flow cytometry and reverse transcriptase-polymerase chain reaction (PCR) or real-time PCR, respectively. Results. CD68+ lining macrophages, like the vasculature, expressed high levels of RAGE in inflamed ST from RA patients. RAGE mRNA expression was significantly higher in RA ST than in ST from patients with osteoarthritis. RAGE mRNA levels were significantly higher in ST macrophages and normal endothelial cells than in ST CD4+ T cells and synovial fibroblasts stimulated with tumor necrosis factor α and interleukin-l (IL-1β). Cell surface RAGE was highly induced on normal monocytes after a 24-hour incubation with a 20% concentration of RA ST cell culture supernatants. RAGE mRNA expression in adherent monocytes was augmented by various cytokines, most potently by IL-1β. Conclusion. These results indicate that RAGE overexpression in lining macrophages may be induced, at least in part, by cytokines such as IL-1, leading to the amplification of inflammatory responses mediated by RAGE ligands that are abundant in RA joints.
UR - http://www.scopus.com/inward/record.url?scp=31044445707&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=31044445707&partnerID=8YFLogxK
U2 - 10.1002/art.21524
DO - 10.1002/art.21524
M3 - Article
C2 - 16385501
AN - SCOPUS:31044445707
VL - 54
SP - 97
EP - 104
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 1
ER -