PubMed · 15926776
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Bill Saporito. 2005-05-23. My most difficult choice.. https://pubmed.ncbi.nlm.nih.gov/15926776/
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OBJECTIVE: To explore the underlying mechanism of lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and IL-6 release via p38 mitogen-activated protein kinase (MAPK) pathway in HeLa cells for further identification of involved down-stream message factors. METHODS: HeLa cells were challenged with LPS to reproduce inflammatory cell model. The activity or expression of p38 MAPK, cytosolic phospholipase A(2) (cPLA(2)) and COX-2, was inhibited with pretreatment of inflammatory HeLa cells with the inhibitors (SB203580, AACOCF(3), NS-398) or transfected with the cPLA(2) antisense oligonucleotide (SK7111), then the activities and/or expression of p38 MAPK, cPLA(2), COX-2, and relationship with levels of IL-1 beta and IL-6 supernatants were determined in each group. RESULTS: SB203580 obviously down-regulated the activities of p38 and cPLA(2), as well as the release of IL-1 beta and IL-6. AACOCF(3) and SK7111 blocked dose-dependently the activity or expression of cPLA(2), IL-1 beta and IL-6 production. However, the expression of COX-2 could hardly be detected in HeLa cells, even after LPS treatment. At the same time, pre-treatment with NS-398 had no effect on IL-1 beta, IL-6 production. CONCLUSION: p38 MAPK/cPLA(2) pathway mediates the expression of IL-1 beta and IL-6 resulting from LPS treatment of HeLa cells, while COX-2, as a down-stream enzyme of cPLA(2) has no effect in this process.
Angiogenesis is essential for development, growth and advancement of solid tumors. Cyclooxygenase (COX)-2 is recognized as an angiogenic factor in various tumors. This prompted us to study the clinical implications of COX-2 expression related to angiogenesis in uterine cervical cancers. There was a significant correlation between microvessel counts and COX-2 levels in uterine cervical cancers. COX-2 localized in the cancer cells, but not in the stromal cells of uterine cervical cancer tissues. COX-2 levels increased with advancement, and the prognosis of the 30 patients with high COX-2 expression in uterine cervical cancers was poor (60%), while the 24-month survival rate of the other 30 patients with low COX-2 expression was 90%. Furthermore, COX-2 levels significantly correlated with VEGF levels in uterine cervical cancers. VEGF associated with COX-2 might work on angiogenesis in advancement. Therefore, long-term administration of COX-2 inhibitors might be effective on the suppression of regrowth or recurrence after intensive treatment for advanced uterine cervical cancers.
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.