Human alveolar macrophages have both lipopolysaccharide (LPS)-induced and constitutive phosphatidylinositol 3-kinase (PI3K) activity. We observed that blocking PI3K activity increased release of prostaglandin E2 after LPS exposure, and increasing PI3K activity (interleukin-13) decreased release of prostaglandin E2 after LPS exposure. This was not because of an effect of PI3K on phospholipase 2 activity. PI3K inhibition resulted in an increase in cyclooxygenase 2 (COX2) protein, mRNA, and mRNA stability. PI3K negatively regulated activation of the p38 pathway (p38, MKK3/6, and MAPKAP2), and an active p38 was necessary for COX2 production. The data suggest that PI3K inhibition of p38 modulates COX2 expression via destabilization of LPS-induced COX2 mRNA.
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Monick, M. M., Robeff, P. K., Butler, N. S., Flaherty, D. M., Brent Carter, A., Peterson, M. W., & Hunninghake, G. W. (2002). Phosphatidylinositol 3-kinase activity negatively regulates stability of cyclooxygenase 2 mRNA. Journal of Biological Chemistry, 277(36), 32992–33000. https://doi.org/10.1074/jbc.M203218200