Abstract
Using in situ hybridization, RT-PCR, lectin histochemistry and immunohistochemistry, this study examined the time course expression and cellular localization of various cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-1, IL-6) and transforming growth factor-beta (TGF-beta) in fetal rat brain after a maternal injection of the teratogen cyclophosphamide (CP). Eight hours after CP injection, there was a marked increase in brain macrophages (BM)/amoeboid microglia (AM) in different areas of the fetal brain as determined by lectin histochemistry. Concomitant to this was the induction in mRNA level of TNF-alpha, which was progressively increased with time. TGF-beta mRNA was undetectable until 24 h had elapsed. Expression of IL-1 and IL-6 was undetectable at all stages. In situ hybridization combined with immunohistochemistry has shown the localization of TNF-alpha in BM/AM and neurons. Present results suggest that both TNF-alpha and TGF-beta are involved in the progression of neural damage in the fetal brain induced by the teratogen.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD*
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Antigens, Neoplasm*
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Antigens, Surface*
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Avian Proteins*
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Basigin
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Blood Proteins*
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Brain / drug effects*
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Brain / embryology
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Brain / immunology
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Cell Movement / drug effects
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Cell Movement / immunology
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Cyclophosphamide / pharmacology
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Cytokines / genetics
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Cytokines / immunology
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Cytokines / metabolism*
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Female
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Fetus / drug effects*
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Fetus / embryology
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Fetus / immunology
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / physiology
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Interleukin-1 / genetics
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Interleukin-1 / immunology
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Interleukin-1 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / immunology
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Interleukin-6 / metabolism
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Lectins / pharmacokinetics
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Macrophages / drug effects*
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Macrophages / immunology
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Macrophages / metabolism
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Membrane Glycoproteins / metabolism
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Microglia / drug effects*
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Microglia / immunology
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Microglia / metabolism
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Mutagens / pharmacology
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Pregnancy
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Prenatal Exposure Delayed Effects*
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Reverse Transcriptase Polymerase Chain Reaction
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Teratogens / pharmacology*
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Time Factors
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / immunology
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Transforming Growth Factor beta / metabolism
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antigens, CD
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Antigens, Neoplasm
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Antigens, Surface
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Avian Proteins
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Blood Proteins
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Bsg protein, Gallus gallus
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Bsg protein, rat
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Cytokines
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Interleukin-1
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Interleukin-6
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Lectins
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Membrane Glycoproteins
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Mutagens
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RNA, Messenger
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Teratogens
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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Basigin
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Cyclophosphamide