JOHNSON, Rodney W.

Department of Animal Sciences
Ph.D. (1992) University Illinois

   Research Topics

• Regulation of cytokine gene expression in aged brain

• Inflammatory cytokines in anorexia and cachexia

• Regulation of sickness behavior

   Research Interests  

   Our research is concerned with the behavioral, metabolic, and neurobiologic effects of inflammatory cytokines.  Activated mononuclear myeloid cells in both the periphery (i.e., macrophages) and central nervous system (i.e., microglia) synthesize and secrete the inflammatory cytokines interleukin-1, interleukin-6 and tumor necrosis factor-a.  These molecules act on specific receptors located in disparate physiological systems including the brain to coordinate the host's response to immunological challenge.  For example, when present in the central nervous system cytokines alter the neuroendocrine system and induce anorexia, thermogenesis, hypersomnia, and malaise.  If unregulated, inflammatory cytokines also lead to neurodegeneration.  A special focus of our research is to understand how inflammatory cytokines in the brain are regulated and the role of brain cytokines in anorexia and cachexia in aging and in disease.  We use molecular, cellular and whole animal approaches to study the underlying mechanisms of cytokine-induced anorexia and cachexia. One in vivo approach involves stereotaxic placement of a cannula in a lateral cerebral ventricle of adult and aged mice for central injection of recombinant cytokines or cytokine antagonists.  Because microglial cells are the principal source of inflammatory cytokines in the brain, another approach we use involves establishing highly purified microglial cell cultures from murine brain.  We have used these cells, for example, to study the effects of aging on the transcription factors that regulate the interleukin-6 gene.  The underlying goal of this research is to understand how inflammatory cytokines are regulated in the brain so that novel strategies can be developed to either prevent or treat the anorexia, cachexia, and neurodegeneration that often occur in disease and in aging.

   Key Words   Recombinant DNA, Gene Expression Systems, Cellular Immunology, Lymphokines/Growth Factors, Disease Models, Animal Cell and/or Tissue Culture, Transgenic Animals, DNA-Protein Interactions, Neurobiology, Hormones

   Current Research Funding   NIH (NIDDKD & NIA