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Involvement of prostaglandin E 2 released from leptomeningeal cells in increased expression of transforming growth factor‐β in glial cells and cortical neurons during systemic inflammation
Author(s) -
Wu Zhou,
Hayashi Yoshinori,
Zhang Jian,
Nakanishi Hiroshi
Publication year - 2007
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21100
Subject(s) - inflammation , transforming growth factor , microbiology and biotechnology , prostaglandin , prostaglandin e2 , neuroscience , prostaglandin e , chemistry , cancer research , biology , immunology , endocrinology
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 E 2 (PGE 2 ) 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 PGE 2 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. PGE 2 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. © 2006 Wiley‐Liss, Inc.