The MAPK superfamily of serine/threonine kinases has indeed emerged as an important component of cellular signal transduction, activated by phosphorylation on both threonine and tyrosine residues. In fact, numerous evidence support the MAPKs as playing a key role in regulating not only cell proliferation, apoptosis, migration, and differentiation [29], [30] and [31], but the
KX2-391 of many proinflammatory genes implicated in the development of atherosclerosis as well [32], [33], [34], [35] and [36]. It has been reported that three MAPK cascades (p38, ERK1/2, and JNK) were involved in the MMP-9 induction by PMA [37], [38] and [39]. Interestingly, we determined the activation of the p38 and ERK1/2 pathways as both necessary for EMMPRIN expression to regulate the production of MMPs. Concerning this, M. Lim et al. [8] reported that tumor-derived EMMPRIN stimulates MMP-1
expression through the p38 pathway. Therefore, MAPKs play important roles in the regulation of both EMMPRIN and MMPs. Also worth mentioning is that, according to Carter et al. [40], PMA activates both the ERK1/2 and JNK pathways in THP-1 cells, with a failure of activation of the p38 pathway. This report, however, is not in agreement with our result. In their experiment, they chose to assess p38 phosphorylation at 15 min. Our study, on the other hand, observed p38 phosphorylation peaks at 5 min, which then declined after 10 min. Thus, the discrepancy could be due to Carter’s longer period of assessing p38 activation.
