Transforming growth factor-β1 induces transforming growth factor-β1 and transforming growth factor-β receptor messenger RNAs and reduces complement C1qB messenger RNA in rat brain microglia

T. E. Morgan, I. Rozovsky, Dipak Sarkar, C. S. Young-Chan, N. R. Nichols, N. J. Laping, C. E. Finch

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Transforming growth factor-β1 is a multifunctional peptide with increased expression during Alzheimer's disease and other neurodegenerative conditions which involve inflammatory mechanisms. We examined the autoregulation of transforming growth factor-β1 and transforming growth factor-β receptors and the effects of transforming growth factor-β1 on complement C1q in brains of adult Fischer 344 male rats and in primary glial cultures. Perforant path transection by entorhinal cortex lesioning was used as a model for the hippocampal deafferentation of Alzheimer's disease. In the hippocampus ipsilateral to the lesion, transforming growth factor-β1 peptide was increased > 100-fold; the messenger RNAs encoding transforming growth factor-β1, transforming growth factor-β type I and type II receptors were also increased, but to a smaller degree. In this acute lesion paradigm, microglia are the main cell type containing transforming growth factor-β1, transforming growth factor-β type I and II receptor messenger RNAs, shown by immunocytochemistry in combination with in situ hybridization. Autoregulation of the transforming growth factor-β1 system was examined by intraventricular infusion of transforming growth factor-β1 peptide, which increased hippocampal transforming growth factor-β1 messenger RNA levels in a dose-dependent fashion. Similarly, transforming growth factor-β1 increased levels of transforming growth factor-β1 messenger RNA and transforming growth factor-β type II receptor messenger RNA (IC50, 5 pM) and increased release of transforming growth factor-β1 peptide from primary microglia cultures. Interactions of transforming growth factor-β1 with complement system gene expression are also indicated, because transforming growth factor-β1 decreased C1qB messenger RNA in the cortex and hippocampus, after intraventricular infusion, and in cultured glia. These indications of autocrine regulation of transforming growth factor-β1 in the rodent brain support a major role of microglia in neural activities of transforming growth factor-β1 and give a new link between transforming growth factor-β1 and the complement system. The auto-induction of the transforming growth factor-β1 system has implications for transgenic mice that overexpress transforming growth factor-β1 in brain cells and for its potential role in amyloidogenesis. (C) 2000 IBRO.

Original languageEnglish (US)
Pages (from-to)313-321
Number of pages9
JournalNeuroscience
Volume101
Issue number2
DOIs
StatePublished - Nov 7 2000

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Keywords

  • Auto-induction
  • Inflammation
  • Perforant path transection

Fingerprint Dive into the research topics of 'Transforming growth factor-β1 induces transforming growth factor-β1 and transforming growth factor-β receptor messenger RNAs and reduces complement C1qB messenger RNA in rat brain microglia'. Together they form a unique fingerprint.

Cite this