BDNF and Other Neutrophic Factors May Prevent Seizures and Assoc. Inflammation!

Bovolenta, R. et al. Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures. Journal of neuroinflammation 7, 81+ (2010). URL http://dx.doi.org/10.1186/1742-2094-7-81.

GSK-3b and the Inflammatory Response in Environmental Illnesses

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:

• SIRT1 regulates the expression of HSF which can be elevated by resveratrol.

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

Epstein Barr: Interesting Interactions With Inflammatory Mediators Implicated in Environmental Illness

Summary: This nuclear translocation of NF-kappaB may promote viral latency by negatively regulating BZLF1 transcriptional activity. In situations where p65 activity is limiting in comparison to BZLF1, the ability of BZLF1 to inhibit p65 transcriptional function may protect the virus from the host immune system during the lytic form of infection.


Morrison, T. E. and Kenney, S. C. (2004). Bzlf1, an epstein-barr virus immediate-early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function. Virology, 328(2):219-232. http://www.citeulike.org/user/HEIRS/article/6463038

Interleukin-1 is essential for systemic inflammatory bone loss

Interleukin-1 is essential for systemic inflammatory bone loss: "URL: Interleukin-1 is essential for systemic inflammatory bone loss

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Interleukin-1 receptor antagonist inhibits the release of glutamate, hydroxyl radicals, and prostaglandin E2 in the hypothalamus during pyrogen-induced fever in rabbits.

Interleukin-1 receptor antagonist inhibits the release of glutamate, hydroxyl radicals, and prostaglandin E2 in the hypothalamus during pyrogen-induced fever in rabbits.: "URL: Interleukin-1 receptor antagonist inhibits the release of glutamate, hydroxyl radicals, and prostaglandin E2 in the hypothalamus during pyrogen-induced fever in rabbits.

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Title: Association of variation in the interleukin-1 gene family with diabetes and glucose homeostasis. The Journal of clinical endocrinology and metabolism.

Summary: Specific haplotypes of Il-1b are associated with higher glucose, higher insulin resistance. higher insulin and increased prevalence of diabetes.

Citation: Luotola, K., Pääkkönen, R., Alanne, M., Lanki, T., Moilanen, L., Surakka, I., Pietilä, A., Kähönen, M., Nieminen, M. S., Kesäniemi, Y. A., Peters, A., Jula, A., Perola, M., Salomaa, V., and for the Health 2000 and AIRGENE Study Groups (2009). Association of variation in the interleukin-1 gene family with diabetes and glucose homeostasis. The Journal of clinical endocrinology and metabolism. http://www.citeulike.org/user/HEIRS/article/5938589

Fats Interact With Immune Complex to Activate Inflammation -May Aggravate Autoimmune and Pathogen Infection

HEIRS Environmental Illness Research Blog: Infection/Endotoxin in Chronic Fatigue, Fibromyalgia and Multiple Chemical Sensitivity.

The interaction between toll-like receptors and fatty acids "engage" the immune complex Il-1b and its receptor to activate other inflammatory processes in the pancreas.



Böni-Schnetzler, M., Boller, S., Debray, S., Bouzakri, K., Meier, D. T., Prazak, R., Kerr-Conte, J., Pattou, F., Ehses, J. A., Schuit, F. C., and Donath, M. Y. (2009). Free fatty acids induce a proinflammatory response in islets via the abundantly expressed interleukin-1 receptor i. Endocrinology, pages en.2009-0543+. http://www.citeulike.org/user/HEIRS/article/5922922

Nitrosamines and PGC-1a

PGC-1a is an important component for the detoxification of nitrosamines. Excess levels can lead to enhanced toxicity. A recent study shows nitrosamine increases oxidative and nitrosative stress and elevates inflammatory mediators including Tnf-a , MCP-1 and Il-1 by activation of microglia and astrocytes resulting in neuronal damage. Nitrosamines are chemical compounds which are produced from nitrites and secondary amines. Some are carcinogenic are can be produced from certain methods of cooking and are also in beer and latex. (Wipedia)




Ghosh, D., Mishra, M. K. K., Das, S., Kaushik, D. K. K., and Basu, A. (2009). Tobacco carcinogen induces microglial activation and subsequent neuronal damage. Journal of neurochemistry, 110(3):1070-1081. http://www.citeulike.org/user/HEIRS/article/5202108
Nitrosamines. Wipedia. Retrieved on September 6, 2009.