Changes of nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in human myometrium before and during term labor

Objective: To investigate the changes of nuclear factor kappa B (NF-kappa B), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in human term myometrium before and during term labor. Study design: Myometrium was obtained from women undergoing cesarean delivery at term before (n = 16) and after labor (n = 12). Immunostaining of NF-kappa B subunits (p65/p5O) and Western blot analysis of NF-kappa B subunits, MMP-9 and COX-2 proteins were compared. Human term myocyte cultures were stimulated with IL-l beta. Activation of NF-kappa B was assessed by evaluating changes in the inhibitory protein I kappa B; regulation of COX-2 and MMP-9 levels was studied using Western blot analysis and gelatin zymography. Results: In contrast to a significant increase in the level of COX-2 and MMP-9 proteins, p65 and p50 decreased significantly in the after-labor group compared to the before-labor group. After treatment with IL-1 beta I kappa B was degraded by almost 90% within 5 min and became undetectable by 15 min. IL-1 beta stimulation increased the levels of COX-2 protein and the gelatinolytic activities of MMP-9, both of which were inhibited by NF-kappa B inhibitors. Conclusions: Human term labor is associated with changes in NF-kappa B and increased expression of COX-2 and MMP-9 in the myometrium. NF-kappa B pathway activation and subsequent increments of COX-2 and MMP-9 were observed in human term myocyte cultures. (C) 2006 Elsevier Ireland Ltd. All rights reserved.