Objective: To investigate the changes of nuclear factor kappa B (NF-kappaB), 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-kappaB subunits (p65/p50) and Western blot analysis of NF-kappaB subunits, MMP-9 and COX-2 proteins were compared. Human term myocyte cultures were stimulated with IL-1beta. Activation of NF-kappaB was assessed by evaluating changes in the inhibitory protein IkappaB; 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-1beta, IkappaB was degraded by almost 90% within 5 min and became undetectable by 15 min. IL-1beta stimulation increased the levels of COX-2 protein and the gelatinolytic activities of MMP-9, both of which were inhibited by NF-kappaB inhibitors.
Conclusions: Human term labor is associated with changes in NF-kappaB and increased expression of COX-2 and MMP-9 in the myometrium. NF-kappaB pathway activation and subsequent increments of COX-2 and MMP-9 were observed in human term myocyte cultures.