Induction of cytokine expression in the brain macrophages/amoeboid microglia of the fetal rat exposed to a teratogen.
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.
Hao
A J
AJ
Department of Anatomy, Faculty of Medicine, National University of Singapore, Republic of Singapore.
Dheen
S T
ST
Ling
E A
EA
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000196:embryology / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D037102:Lectins / Q000493:pharmacokinetics; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D009153:Mutagens / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013723:Teratogens / Q000494:pharmacology*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D037102:Lectins; D008562:Membrane Glycoproteins; D009153:Mutagens; D012333:RNA, Messenger; D013723:Teratogens; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D051926:Basigin; D003520:Cyclophosphamide