Histamine stimulates matrix metalloproteinase-3 and -13 production by human articular chondrocytes in vitro.
OBJECTIVE
To determine the effects of histamine on matrix metalloproteinase (MMP) production by human articular chondrocytes (HAC) in vitro.


METHODS
Conditioned culture medium from HAC cultures incubated with and without 20 microM histamine was assayed by enzymne linked immunosorbent assay (ELISA) for MMP-1, MMP-8, MMP-13 (collagenases 1, 2, and 3, respectively) and MMP-3 (stromelysin). Monolayer cultures of HAC were also immunostained for MMP-13 and MMP-3.


RESULTS
The HAC cultures showed a significant increase in MMP-13 and MMP-3 production (2.2- and 1.9-fold, respectively) after treatment with 20 microM histamine for 24 hours, but MMP-1 and MMP-8 were unaffected. All cultures showed MMP-13 and MMP-3 detectable by immunolocalisation. MMP-3 was the more prominent enzyme as shown by both ELISA and immunolocalisation techniques.


CONCLUSIONS
Histamine exposure increased both MMP-13 and MMP-3 production by HAC in vitro, thereby suggesting a pathophysiological role in the chondrocytic phenotype associated with degenerative changes in osteoarthritis.
Tetlow
L C
LC
University Department of Medicine, Manchester Royal Infirmary, Oxford Road, UK. lynne.c.tetlow@man.ac.uk
Woolley
D E
DE
D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*
D006632:Histamine; D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3