title: Transforming growth factor beta expression in reactive spinal cord microglia and meningeal inflammatory cells during experimental allergic neuritis.
abstract: 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)
authors.affiliation: Department of Neuromorphology, Max-Planck Institute for Psychiatry, Martinsried, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kiefer
authors.forename: R
authors.initials: R
authors.lastname: Gold
authors.forename: J
authors.initials: J
authors.lastname: Gehrmann
authors.forename: D
authors.initials: D
authors.lastname: Lindholm
authors.forename: H
authors.initials: H
authors.lastname: Wekerle
authors.forename: G W
authors.initials: GW
authors.lastname: Kreutzberg
mesh_terms: 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*
chemical_list: D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta