Are mAPKs essential upstream signaling pathways in proteolytic cartilage degradation -- divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation?
We found that inhibition of MAPK P38, P44/42 and Src family abrogated proteolytic cartilage degradation by blocking MMP synthesis and activity. However, only MAPK P44/42 was essential for aggrecanase-mediated aggrecan degradation. These data suggest that various aspects of cartilage degradation can be targeted independently by inhibiting specific upstream signaling pathway.
Mature DCs cocultured with ovarian cancer ascites or supernatants of SKOV3 and CAOV3 differentiated into a group of macrophagelike cells that exhibited increased expression of surface marker CD14+CD1a-, decreased expression of CD83, poorer T-cell costimulatory properties, and greater endocytosis of fluorescein isothiocyanate-dextran in vitro. Interleukin 10 but not LIF mediated this differentiation pathway.