Some experts believe that Il-6 is an important cytokine in the activation of autoimmune and inflammatory diseases, some forms of cancer and present at high levels in PTSD. GSK-3b has been our recent topic of discussion and some important considerations for the actions of this protein is its overexpression may contribute to a number of mental and physical health conditions. Its activities provide a sort-of "on-off" switch for the antioxidant system Nrf2 and inhibits the expression of PGC-1 and for this reason is an important regulator of cellular homeostasis and energy metabolism. It has also been demonstrated GSK-3b inhibits heat shock factor which has important implications for studies of lifespan. Heat shock factor assists in the control of stress response activation through heat shock proteins which have protective properties that "aid in folding, transport, regulation, and degradation of cellular proteins under normal conditions, and their expression during stress is essential for cell survival." (Xavier) Heat shock factor has the ability to "repress" the expression of Il-1 through a transcription mechanism associated with Il-6 and thereby, limiting inflammatory responses. (Xie) These studies suggest that overexpression of GSK-3b (ie. that may occur from endotoxin-induced production of Tnf-a) may contribute to activation of immune responses that are "autoimmune or inflammatory" in nature. It also provides more evidence of the role of Nrf2 in autoimmune-type responses and that inhibition of PGC-1a may contribute to dysregulation of metabolism associated with environmental illness.
Notes:
Xavier et al. Glycogen Synthase Kinase 3B Negatively Regulates Both DNA-Binding and Transcriptional Activities of Heat Shock Factor 1. June 2000. http://www.citeulike.org/user/HEIRS/article/6590895
Ishihara, K. and Hirano, T. (2002). Il-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine & growth factor reviews, 13(4-5):357-368. http://www.citeulike.org/user/HEIRS/article/4365589
Maes, M. (1999). Elevated serum interleukin-6 (il-6) and il-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events. Biological Psychiatry, 45(7):833-839. http://www.citeulike.org/user/HEIRS/article/4509997
Xie, Y., Chen, C., Stevenson, M. A., Auron, P. E., and Calderwood, S. K. (2002). Heat shock factor 1 represses transcription of theil-1β gene through physical interaction with the nuclear factor of interleukin 6. Journal of Biological Chemistry, 277(14):11802-11810. http://www.citeulike.org/user/HEIRS/article/6590793
Handschin, C., Chin, S., Li, P., Liu, F., Maratos-Flier, E., Lebrasseur, N. K., Yan, Z., and Spiegelman, B. M. (2007). Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in pgc-1 alpha muscle-specific knock-out animals. The Journal of biological chemistry, 282(41):30014-30021. http://www.citeulike.org/user/HEIRS/article/1907765
Corton, J. C. and Brown-Borg, H. M. (2005). Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric restriction and other models of longevity. J Gerontol A Biol Sci Med Sci, 60(12):1494-1509. http://www.citeulike.org/user/HEIRS/article/2339648
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