Involvement of prostaglandin E2 released from leptomeningeal cells in increased expression of transforming growth factor-beta in glial cells and cortical neurons during systemic inflammation.
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-beta1 (TGF-beta1) 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-beta1 and TGF-beta receptor II (TGF-betaRII) both markedly increased in the leptomeninges and the parenchymal cells after the CFA injection. Double-staining immunohistochemistry demonstrated TGF-beta1 to be induced in both glial cells and cortical neurons, whereas TGF-betaRII 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-beta1 and TGF-betaRII 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-beta1 and TGF-betaRII in the primary cultured cells. These observations strongly suggest that PGE(2), which is biosynthesized by the leptomeninges, mainly regulates the production of TGF-beta1 by glial cells and cortical neuron, thus playing a protective role in the cortical neurons during systemic inflammation. Furthermore, TGF-beta1 may also exert a protective effect directly on the cortical neurons.
Wu
Zhou
Z
Laboratory of Oral Aging Science, Faculty of Dental Sciences, Kyushu University, Fukuoka, Japan.
Hayashi
Yoshinori
Y
Zhang
Jian
J
Nakanishi
Hiroshi
H
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000008:administration & dosage; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005620:Freund's Adjuvant; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008578:Meninges / Q000166:cytology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D052246:Cyclooxygenase 2 Inhibitors; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta; D005620:Freund's Adjuvant; D051546:Cyclooxygenase 2; D015232:Dinoprostone