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Suppression of matrix metalloproteinase-3 synthesis by interleukin-4 in human articular chondrocytes
O Nemoto1, H Yamada, T Kikuchi
1Department of Orthopaedic Surgery, National Defense Medical College, Saitama, Japan.
Objective:
To evaluate the effect of interleukin-4 (IL-4) on IL-1 induced matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) production by human articular chondrocytes.
Methods:
Monolayer cell culture of chondrocytes was obtained from human articular cartilage from patella within 24 h after death. MMP-3 and TIMP-1 protein levels were determined by ELISA. MMP-3 activity was assayed as caseinase activity. Amounts of MMP-3 and TIMP-1 mRNA were measured by Northern blot analysis.
Results:
IL-4 suppressed IL-1 stimulated MMP-3 protein and enzyme activity. Moreover, IL-4 suppressed IL-1 induced MMP-3 mRNA. In contrast, IL-4 did not alter the level of TIMP-1 protein and mRNA.
Conclusion:
IL-4 may be implicated as a protective mediator of joint destruction seen in inflammatory arthritis.
Insights
Interleukin-4 (IL-4) reduces interleukin-1 (IL-1) stimulated matrix metalloproteinase-3 (MMP-3) production in human cartilage cells. This suggests IL-4 may protect against joint destruction in inflammatory arthritis.
Area of Science:
- Biochemistry
- Immunology
- Cell Biology
Background:
- Inflammatory arthritis involves joint destruction.
- Matrix metalloproteinases (MMPs), like MMP-3, contribute to cartilage degradation.
- Interleukin-1 (IL-1) stimulates MMP production in chondrocytes.
Purpose of the Study:
- To investigate the effect of interleukin-4 (IL-4) on IL-1 induced production of MMP-3 and TIMP-1 in human articular chondrocytes.
Main Methods:
- Human articular chondrocytes were cultured.
- MMP-3 and TIMP-1 protein levels were measured using ELISA.
- MMP-3 activity was assessed via caseinase activity.
- MMP-3 and TIMP-1 mRNA levels were analyzed by Northern blot.
Main Results:
- IL-4 significantly suppressed IL-1 stimulated MMP-3 protein levels and enzyme activity.
- IL-4 also reduced IL-1 induced MMP-3 mRNA expression.
- IL-4 did not affect TIMP-1 protein or mRNA levels.
Conclusions:
- IL-4 exhibits a suppressive effect on IL-1 induced MMP-3 production in chondrocytes.
- IL-4 may play a protective role in mitigating joint damage associated with inflammatory arthritis.