Suppression of matrix metalloproteinase-3 synthesis by interleukin-4 in human articular chondrocytes.
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.


CONCLUSIONS
IL-4 may be implicated as a protective mediator of joint destruction seen in inflammatory arthritis.
Nemoto
O
O
Department of Orthopaedic Surgery, National Defense Medical College, Saitama, Japan.
Yamada
H
H
Kikuchi
T
T
Shinmei
M
M
Obata
K
K
Sato
H
H
Seiki
M
M
Shimmei
M
M
D000328:Adult; D002358:Cartilage, Articular / Q000187:drug effects* / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D011480:Protease Inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D006133:Growth Substances; D007375:Interleukin-1; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D015847:Interleukin-4; D008666:Metalloendopeptidases; C030895:caseinase; D019278:Matrix Metalloproteinase 3