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

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• Hypertonic saline solution (HTS) and lipopolysaccharide (LPS) were previously shown to induce prostacyclin (PGI(2)) production in human endothelial cells.
• This study investigated whether HTS and LPS increase PGI(2) via cyclooxygenase (COX) expression and the role of p38 and ERK signaling pathways.

Purpose of the Study:

• To determine if HTS and LPS upregulate cyclooxygenase (COX) expression, specifically COX-2.
• To investigate the involvement of p38 and extracellular signal-regulated kinases (ERK) signaling pathways in mediating COX expression and PGI(2) production.

Main Methods:

• Human umbilical vein endothelial cells were stimulated with varying concentrations of NaCl (hypertonic saline) or LPS.
• Cellular responses including p38 and ERK activation, COX-1 and COX-2 expression, and PGI(2) production were measured.
• Specific inhibitors were used to block p38 and ERK pathways.

Main Results:

• HTS and LPS induced rapid activation of p38 and ERK signaling pathways.
• A dose-dependent increase in COX-2 expression was observed with HTS and LPS, correlating with elevated PGI(2) levels.
• Inhibition of p38 abrogated both COX-2 expression and PGI(2) production, while ERK inhibition had no significant effect.

Conclusions:

• Hyperosmolarity and LPS sequentially activate p38 and ERK, leading to COX-2 expression and subsequent PGI(2) production.
• Increased COX-2 expression is a key mechanism for elevated PGI(2) synthesis under these conditions.
• The p38 mitogen-activated protein kinase pathway plays a significant role in the signaling cascade regulating COX-2 expression.