Involvement of prostaglandin E2 released from leptomeningeal cells in increased expression of transforming growth factor-β in glial cells and cortical neurons during systemic inflammation

Zhou Wu, Yoshinori Hayashi, Jian Zhang, Hiroshi Nakanishi

研究成果: Contribution to journalArticle査読

25 被引用数 (Scopus)

抄録

The leptomeninges play a central role in the antiinflammatory response through the glia-neuron interaction during systemic inflammation. In the present study, we examined the possible production of two potent antiinflammatory mediators, prostaglandin E2 (PGE2) and transforming growth factor-β1 (TGF-β1) by leptomeningeal cells during systemic inflammation. After immunization with the complete Freund's adjuvant (CFA), cyclooxygenase (COX)-2 and membrane-bound PGE synthase-1 (mPGES-1) were induced in the leptomeninges. Primary cultured leptomeningeal cells secreted PGE 2 after treatment with lipopolysaccharide (LPS) or proinflammatory cytokines. The LPS-induced release of PGE2 was depressed by a selective COX-2 inhibitor, NS-398. On the other hand, TGF-β1 and TGF-β receptor II (TGF-βRII) both markedly increased in the leptomeninges and the parenchymal cells after the CFA injection. Double-staining immunohistochemistry demonstrated TGF-β1 to be induced in both glial cells and cortical neurons, whereas TGF-βRII was induced only in cortical neurons. Furthermore, the conditioned medium prepared from the leptomeningeal cells after LPS stimulation was able to induce an increased expression of TGF-β1 and TGF-βRII in the primary cultured glial cells and cortical neurons. This increased expression was suppressed by NS-398. PGE2 was found to increase directly the production of TGF-β1 and TGF-βRII in the primary cultured cells. These observations strongly suggest that PGE 2, which is biosynthesized by the leptomeninges, mainly regulates the production of TGF-β1 by glial cells and cortical neuron, thus playing a protective role in the cortical neurons during systemic inflammation. Furthermore, TGF-β1 may also exert a protective effect directly on the cortical neurons.

本文言語英語
ページ(範囲)184-192
ページ数9
ジャーナルJournal of Neuroscience Research
85
1
DOI
出版ステータス出版済み - 1 2007

All Science Journal Classification (ASJC) codes

  • 細胞および分子神経科学

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