Abbreviations: COX, cyclooxygenase; ECM, extracellular matrix; ERK, extracellular signal-regulated kinase; MAPK, mitogen activated protein kinase; MMP, matrix metalloproteinase; PKC, protein kinase C A bstract IL-1β is know n prom ote cyclooxygenase-2 (C O X-2) an d m atrix m etallo p ro tein ase-2 (M M P -2) expressio n. T his stu dy focuses o n the characterization o f the sig naling cascad e asso ciated w ith IL -1β-in duced m atrix m etallop rotein ase-2 (M M P -2) regu lation in hu m an ch

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... ond rocytes. T he decrease in co llag en levels in th e co n d itio n ed m edia w as prevented by a broad spectrum M M P inh ibitor, sugg esting that IL -1β prom o tes th e proteolytic process leading to M M P -2 activation. IL-1β-related M M P -2 expression w as found to be depend en t on p rostagland in E 2 (P G E 2) prod uction. In add itio n, the in duction of C O X -2 and M M P -2 w as in hibited by the pretreatm ent of chon drocytes w ith a S B 203580 o r R o 31-8220, ind icating th e involvem ent o f protein kinase C (P K C ) o r p38 m ito gen-activated protein kinase (M A P K ). H o w ever, th ere is n o cro ss-talk b etw een P K C and p38 M A P K in the IL-1β-ind uced M M P -2 activation . Taken to geth er, these results d em o n strated th at IL -1β in duces M M P -2 expression through the P G E2-dependent m echanism in h um an cho ndro cytes.