Transforming growth factor beta expression in reactive spinal cord microglia and meningeal inflammatory cells during experimental allergic neuritis.
Experimental allergic neuritis (EAN), an inflammatory demyelinating disorder of the peripheral nervous system, is preceded and accompanied by a massive microglial reaction in the spinal cord which occurs in the absence of inflammatory cells infiltrating the cord parenchyma. Since transforming growth factor beta (TGF-beta) has been shown to play a beneficial role in experimental autoimmune disease and might be involved in the regulation of glial activity, we have investigated the expression of TGF-beta in EAN spinal cord and nerve root tissue. Adoptive transfer EAN was induced by the injection of neurotogenic T-cells specific for the P2 myelin protein. In normal spinal cord tissue, both TGF-beta 1 and TGF-beta 3 mRNA were constitutively expressed at low levels. Already 3 days following injection of P2-specific T-cells, TGF-beta 1 mRNA levels began to increase, peaked at day 6 at levels about tenfold above normal, and thereafter declined. TGF-beta 3 was induced even earlier with a sharp rise at day 3 and a peak fourfold above normal at day 4. In situ hybridization for TGF-beta 1 performed on spinal cord sections 6 days after injection of cells localized TGF-beta 1 mRNA to many nonneuronal cells with the typical morphology of microglia. In addition, TGF-beta 1 mRNA was observed in the meninges, and massive accumulation of signal was seen over inflammatory cells infiltrating the nerve roots. Our data indicate that TGF-beta 1 and -beta 3 are involved in regulating the glial response in EAN and that activated microglial cells might control their own activity state by expressing TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Kiefer
R
R
Department of Neuromorphology, Max-Planck Institute for Psychiatry, Martinsried, Germany.
Gold
R
R
Gehrmann
J
J
Lindholm
D
D
Wekerle
H
H
Kreutzberg
G W
GW
D000818:Animals; D015870:Gene Expression; D007116:Immunization, Passive; D017403:In Situ Hybridization; D008578:Meninges / Q000378:metabolism / Q000473:pathology*; D017628:Microglia / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000276:immunology; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics*
D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta