Abstract
Prolonged incubation with interleukin-1β (IL-1) induced the release of large amounts of NO and subsequently inhibited DNA synthesis and the biosynthesis and accumulation of proteoglycans in cultured rabbit articular chondrocytes (RAC). IL-1 also inhibited DNA synthesis in bovine aortic endothelial cells (BAE). On the other hand, DNA synthesis in BAE cocultured with RAC was not inhibited by prolonged incubation with IL-1. Moreover, conditioned media from RAC incubated for a long period with IL-1 stimulated DNA synthesis in BAE alone. This growth stimulatory activity was mainly due to the release of basic fibroblast growth factor, a heparin-binding growth factor, into RAC culture. Gelatin zymography of the RAC culture medium revealed that IL-1 increased the production of matrix met alloproteinase-2 (MMP-2) and MMP-9. N(G)-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited all of these actions of IL-1. These results indicate that NO from RAC treated with IL-1 stimulates MMPs, which, in turn, degrade the extracellular matrix produced by RAC, resulting in the release of large amounts of basic fibroblast growth factor stored in the matrix, which then stimulates adjacent BAE proliferation. Thus, NO produced from RAC treated with IL-1 may modulate angiogenesis in the synovium of arthritic patients.
| Original language | English |
|---|---|
| Pages (from-to) | 3729-3737 |
| Number of pages | 9 |
| Journal | Endocrinology |
| Volume | 137 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 1996 |
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ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes : A possible mechanism of pathological neovascularization in arthritis. / Tamura, Tomoo; Nakanishi, Tohru; Kimura, Yusuke; Hattori, Takako; Sasaki, Kazuhiro; Norimatsu, Hiromichi; Takahashi, Kojiro; Takigawa, Masaharu.
In: Endocrinology, Vol. 137, No. 9, 1996, p. 3729-3737.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes
T2 - A possible mechanism of pathological neovascularization in arthritis
AU - Tamura, Tomoo
AU - Nakanishi, Tohru
AU - Kimura, Yusuke
AU - Hattori, Takako
AU - Sasaki, Kazuhiro
AU - Norimatsu, Hiromichi
AU - Takahashi, Kojiro
AU - Takigawa, Masaharu
PY - 1996
Y1 - 1996
N2 - Prolonged incubation with interleukin-1β (IL-1) induced the release of large amounts of NO and subsequently inhibited DNA synthesis and the biosynthesis and accumulation of proteoglycans in cultured rabbit articular chondrocytes (RAC). IL-1 also inhibited DNA synthesis in bovine aortic endothelial cells (BAE). On the other hand, DNA synthesis in BAE cocultured with RAC was not inhibited by prolonged incubation with IL-1. Moreover, conditioned media from RAC incubated for a long period with IL-1 stimulated DNA synthesis in BAE alone. This growth stimulatory activity was mainly due to the release of basic fibroblast growth factor, a heparin-binding growth factor, into RAC culture. Gelatin zymography of the RAC culture medium revealed that IL-1 increased the production of matrix met alloproteinase-2 (MMP-2) and MMP-9. N(G)-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited all of these actions of IL-1. These results indicate that NO from RAC treated with IL-1 stimulates MMPs, which, in turn, degrade the extracellular matrix produced by RAC, resulting in the release of large amounts of basic fibroblast growth factor stored in the matrix, which then stimulates adjacent BAE proliferation. Thus, NO produced from RAC treated with IL-1 may modulate angiogenesis in the synovium of arthritic patients.
AB - Prolonged incubation with interleukin-1β (IL-1) induced the release of large amounts of NO and subsequently inhibited DNA synthesis and the biosynthesis and accumulation of proteoglycans in cultured rabbit articular chondrocytes (RAC). IL-1 also inhibited DNA synthesis in bovine aortic endothelial cells (BAE). On the other hand, DNA synthesis in BAE cocultured with RAC was not inhibited by prolonged incubation with IL-1. Moreover, conditioned media from RAC incubated for a long period with IL-1 stimulated DNA synthesis in BAE alone. This growth stimulatory activity was mainly due to the release of basic fibroblast growth factor, a heparin-binding growth factor, into RAC culture. Gelatin zymography of the RAC culture medium revealed that IL-1 increased the production of matrix met alloproteinase-2 (MMP-2) and MMP-9. N(G)-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited all of these actions of IL-1. These results indicate that NO from RAC treated with IL-1 stimulates MMPs, which, in turn, degrade the extracellular matrix produced by RAC, resulting in the release of large amounts of basic fibroblast growth factor stored in the matrix, which then stimulates adjacent BAE proliferation. Thus, NO produced from RAC treated with IL-1 may modulate angiogenesis in the synovium of arthritic patients.
UR - http://www.scopus.com/inward/record.url?scp=0029814863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029814863&partnerID=8YFLogxK
U2 - 10.1210/en.137.9.3729
DO - 10.1210/en.137.9.3729
M3 - Article
C2 - 8756539
AN - SCOPUS:0029814863
VL - 137
SP - 3729
EP - 3737
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 9
ER -