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Corticotropin Releasing Factor (CRF) Activation of NF-κB-Directed Transcription in Leukocytes

Cellular and Molecular Neurobiology volume 26, pages 1019–1034 (2006)Cite this article

Summary

1. The aim of this study was to test whether CRF enhanced nuclear factor kappa B (NF-κB)-directed gene transcription in leukocytes and the receptor specificity of the effect. Initially, we examined the ability of CRF to modulate an antigen-specific, in vitro antibody response. Since that could be mediated by NF-κB transcription factor activity, we tested CRF in a NF-κB driven luciferase gene expression reporter assay.

2. CRF enhanced the antigen-specific antibody production in a dose- and time-dependent manner. RAW 264.7 macrophage cells and splenocytes stained by immunohistochemistry were positive for CRF receptors and CRF. Expression of both was up-regulated by mitogen treatment of the splenocytes. CRF also enhanced the NF-κB-regulated reporter assay and this could be blocked by a CRF-R1 receptor antagonist.

3. In light of these findings, it seems likely that CRF enhanced the antigen-specific antibody response through the CRF-R1 receptor by elevation of NF-κB activity. This study provides further support for the concept that CRF can act as an immunomodulator mediating neuro-immune interactions.

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ACKNOWLEDGEMENTS

The authors would like to acknowledge the excellent technical assistance of William Dalmeida and Rachel Herron in this study and to thank Dr. Kenner Rice (NIDDK, National Institutes Health) for the generous gift of antalarmin. This research was supported in part by the John Sealy Memorial Endowment Fund and the National Institute of Neurological Disorders and Stroke (NS039974 & NS041495). The paper is dedicated to Dr. Julius Axelrod. The first time I met Dr. Axelrod he was a honored guest at the first International Society for Neuroimmunomodulation meeting at the NIH in 1984 where he was evaluating this new field of research. A couple of years later, he visited Ed Blalock and me in Galveston. It was a pleasant surprise both times how open minded and curious he was about our work. Unlike many others at the time who dogmatically rejected the idea, he was very interested in how it worked and to understand the research's impact. Dr. Axelrod was truly visionary and he will be greatly missed!

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  1. Farhad Hashemi

    Present address: Department of Microbiology, Tehran University of Medical Sciences, Tehran, Iran

  2. Liesl Schott

    Present address: Department of Surgery, Baylor College of Medicine, Houston, Texas, USA

Affiliations

  1. Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, Texas, USA

    Eric M. Smith & Liesl Schott

  2. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA

    Eric M. Smith, Mike Gregg, Farhad Hashemi & Thomas K. Hughes

  3. Department of Emergency Medicine, University of Texas Medical Branch, Galveston, Texas, USA

    Mike Gregg

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Smith, E.M., Gregg, M., Hashemi, F. et al. Corticotropin Releasing Factor (CRF) Activation of NF-κB-Directed Transcription in Leukocytes. Cell Mol Neurobiol 26, 1019–1034 (2006). https://doi.org/10.1007/s10571-006-9040-1

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KEY WORDS:

  • psychoneuroimmunology
  • neuroimmunomodulation
  • lymphocytes
  • CRH
  • antibody
  • mitogenesis
  • antalarmin