The cachectic mediator proteolysis inducing factor activates NF-κB and STAT3 in human Kupffer cells and monocytes

  • Authors:
    • Tammy M. Watchorn
    • Nabil Dowidar
    • Cornelis H.C. Dejong
    • Ian D. Waddell
    • O. James Garden
    • James A. Ross
  • View Affiliations

  • Published online on: October 1, 2005     https://doi.org/10.3892/ijo.27.4.1105
  • Pages: 1105-1111
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Abstract

A novel proteoglycan, proteolysis inducing factor (PIF), is capable of inducing muscle proteolysis during the process of cancer cachexia, and of inducing an acute phase response in human hepatocytes. We investigated whether PIF is able to activate pro-inflammatory pathways in human Kupffer cells, the resident macrophages of the liver, and in monocytes, resulting in the production of pro-inflammatory cytokines. Normal liver tissue was obtained from patients undergoing partial hepatectomy and Kupffer cells were isolated. Monocytes were isolated from peripheral blood. Following exposure to native PIF, pro-inflammatory cytokine production from Kupffer cells and monocytes was measured and the NF-κB and STAT3 transcriptional pathways were investigated using electrophoretic mobility shift assays. We demonstrate that PIF is able to activate the transcription factor NF-κB and NF-κB-inducible genes in human Kupffer cells, and in monocytes, resulting in the production of pro-inflammatory cytokines such as TNF-α, IL-8 and IL-6. PIF enhances the expression of the cell surface molecules LFA-1 and CD14 on macrophages. PIF also activates the transcription factor STAT3 in Kupffer cells. The pro-inflammatory effects of PIF, mediated via NF-κB and STAT3, are important in macrophage behaviour and may contribute to the inflammatory pro-cachectic process in the liver.

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October 2005
Volume 27 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Watchorn TM, Dowidar N, Dejong CH, Waddell ID, Garden OJ and Ross JA: The cachectic mediator proteolysis inducing factor activates NF-κB and STAT3 in human Kupffer cells and monocytes. Int J Oncol 27: 1105-1111, 2005
APA
Watchorn, T.M., Dowidar, N., Dejong, C.H., Waddell, I.D., Garden, O.J., & Ross, J.A. (2005). The cachectic mediator proteolysis inducing factor activates NF-κB and STAT3 in human Kupffer cells and monocytes. International Journal of Oncology, 27, 1105-1111. https://doi.org/10.3892/ijo.27.4.1105
MLA
Watchorn, T. M., Dowidar, N., Dejong, C. H., Waddell, I. D., Garden, O. J., Ross, J. A."The cachectic mediator proteolysis inducing factor activates NF-κB and STAT3 in human Kupffer cells and monocytes". International Journal of Oncology 27.4 (2005): 1105-1111.
Chicago
Watchorn, T. M., Dowidar, N., Dejong, C. H., Waddell, I. D., Garden, O. J., Ross, J. A."The cachectic mediator proteolysis inducing factor activates NF-κB and STAT3 in human Kupffer cells and monocytes". International Journal of Oncology 27, no. 4 (2005): 1105-1111. https://doi.org/10.3892/ijo.27.4.1105