71. Infiltrating PGI2 producing leukocytes mediate neuroprotecitive effect of cyclooxygenase-2 (COX-2)

• DOI: 10.1016/j.bbi.2012.07.095
• Publication Date: 2012-09-07T14:31:16Z
• Authors: Y. An; N. Belevych; Y. Wang; N. Powell; Z. Liu; Q. Chen; N. Quan
• Keywords: 0301 basic medicine; 03 medical and health sciences

We showed previously that COX-2 is induced in the brain by excitotoxin in two distinct cell populations, neurons and non-neuronal cells. When cox-2 gene is selectively deleted in non-neuronal cells in a conditional knockout mouse line (KO), brain injury volumes induced by excitotoxin were nearly twice as large as those in WT controls, suggesting that the COX-2 expression in non-neuronal cells plays a neuroprotective role. In this study, we investigated the cellular and molecular mechanisms underlying COX-2-dependent neuroprotection. Correlated with the smaller lesion in WT mice, PGI2-producing leukocytes were found to infiltrate into the brain parenchyma in and near the site of lesion in WT, but not the KO, mice. At the site of injury, the level of PGI2 increased significantly after excitotoxin injection in WT, but not the KO, mice. In addition, inhibition of the PGI2 synthesis in WT animals induced an increase in the lesion size, whereas injection of PGI2 agonist in the KO mice reduced the lesion size. Further, after receiving adoptive transfer of blood leukocytes from WT mice, PGI2-expressing cells were found at the site of excitotoxic lesion in the KO animals with a concomittant reduction of lesion volume. These data suggest that PGI2 produced by the infiltrating leukocytes mediates the neuroprotective effect of the non-neuronal expression of COX-2.