Hypertonic saline solution induces prostacyclin production by increasing cyclooxygenase-2 expression

Saman Arbabi, Matthew R. Rosengart, Iris Garcia, Ronald V. Maier

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Background. Previously, we demonstrated that hypertonic saline solution (HTS) and endotoxin (lipopolysaccharide [LPS]) induce prostacyclin (PGI2) production in human endothelial cells. Here, we hypothesized that HTS and LPS may induce PGI2 production by increasing cyclooxygenase (COX) expression. We further examined the activation of p38 and extracellular signal-regulated kinases (ERK) and questioned whether these transduction cascades might mediate COX expression. Methods. Human umbilical vein endothelial cells were stimulated with varying concentrations of NaCl or LPS. Results. HTS and LPS induced prompt activation of both p38 and ERKs that peaked at 30 minutes. HTS and LPS also induced a dose-related increase in COX-2 with maximal expression within 4 to 6 hours; there was no change in COX-1. This correlated with an increase in supernatant PGI2 levels, which became statistically significant for NaCl of more than 40 mmol/L and for all LPS doses. The inhibition of p38 with SB202190 abrogated the osmotic and LPS-induced COX-2 expression and PGI2 production. Inhibition of ERK activation had no effect on COX-2 expression. Conclusions. Hyperosmolarity and LPS induce, in chronologic order, p38 and ERK activation, COX-2 expression, and PGI2 production. Because COX is the rate-limiting enzyme in prostaglandin synthesis, it is likely that the increase in PGI2 production is due to, at least in part, the increased COX-2 expression. The data also suggest that p38 mitogen-activated protein kinase is involved in the signaling cascade for COX-2 expression.

Original languageEnglish
Pages (from-to)198-205
Number of pages8
Issue number2
StatePublished - 2000


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