CRH and Tregs in Autoimmunity: Possible Connections to Chemical Sensitivity~!

Background: In earlier posts we described how commensal bacteria in the gut regulates the induction of T regulatory cells called Tregs that are important for immune functions. The loss of which may include autoimmune-type expressions and may be influential in MCS by loss of tolerance. In addition, we have also discussed how cortico-releasing hormone (CRH or CRF) has many effects and tissue targets, can be influenced by odors, may influence addictive-type behaviors and abherrant signaling may lead to altered signaling that can lead to mood disorders and have other negative influences on behaviors. The activation of CRH is part of the stress response and therefore, become an important part of the response to environmental cues. This same response activates the inflammatory cascade and therefore, the existence of one may coincide with the activation of the other. In addition, inflammatory cascades include activation of immune cells including mast cells.

Christy and Brown explain that Tregs are important in autoimmune disease and have the potential upon induction to prevent and reverse these conditions including diabetes and multiple sclerosis. Both of which are now considered to have an environmental connection. In addition the author notes that lupus, another condition with possible environmental triggers, and other autoimmune conditions are not just a loss of Tregs but a condition where other immune cells called Ag-effector cells become resistent to Treg suppression. At this point, one would suggest that other physiological pathways may be involved and this potentiates the non-adaptive conditions that lead to MCS. In other blogs, we have discussed a number of these conditions including nutrition and expression of cytokines, as well as, the expression of Nrf2.

Christy and Brown also present another important factor that very well may influence the development of MCS by contributing to loss of tolerance and that is the production of CRH from mast cells. These cells are often produced from inflammatory reactions such as those conditions that produced and reported from environmental toxin exposure. The authors discuss how the role of CRH produced from these inflammatory cells in basically an uptapped area of immune science. On the other hand, Soderholm does note that mast cells and CRH are implicated in disruptions of barrier function in irritable bowel syndrome and to a degree, it it now understood they are produced in inflamed tissue and increase inflammation. This protein has been implicated in reactions in rheumatoid arthritis and other inflammatory conditions during stress. For this reason, one can suggest that inflammatory conditions and production of mast cells which can produce this protein may contribute to the response and long-term activation can have important effects on downstream targets and participate in autoimmune-type response such as those observed in chemical sensitivities.

Past HEIRS Blogs: Related Tags: CRF , CRH , Nrf2


Christy, A. L. and Brown, M. A. (2007). The multitasking mast cell: Positive and negative roles in the progression of autoimmunity. J Immunol, 179(5):2673-2679.
http://www.citeulike.org/user/HEIRS/article/7357936
McKay, D. M. (2005). Good bug, bad bug: in the case of enteric inflammatory disease does the epithelium decide? Memórias do Instituto Oswaldo Cruz, 100(s1):205-210.

http://www.citeulike.org/user/HEIRS/article/7357955
Teitelbaum, A. A., Gareau, M. G., Jury, J., Yang, P. C., and Perdue, M. H. (2008). Chronic peripheral administration of corticotropin-releasing factor causes colonic barrier dysfunction similar to psychological stress. Am J Physiol Gastrointest Liver Physiol, 295(3):G452-459. http://www.citeulike.org/user/HEIRS/article/7357961

Gram (+) Bacterial Component Strongly Enhances Inflammatory Response in Rheum Arthritis...

CiteULike: Lipoteichoic acid enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, PKCdelta and c-Src dependent pathways.: "Tang, C.-H. H., Hsu, C.-J. J., Yang, W.-H. H., and Fong, Y.-C. C. (2010). Lipoteichoic acid enhances il-6 production in human synovial fibroblasts via tlr2 receptor, pkcdelta and c-src dependent pathways. Biochemical pharmacology, 79(11):1648-1657."

Arthritis: Environmental exposure to hairspray, lipstick, pollution, can trigger autoimmune diseases

Arthritis: Environmental exposure to hairspray, lipstick, pollution, can trigger autoimmune diseases

ScienceDaily (2010-01-27) -- Our immediate environment interacts with our genetic programming and can determine if we will succumb to an autoimmune disease, according to new research. ... > read full article

Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate

CiteULike: Inhibition of synovial hyperplasia, rheumatoid T cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate: "Kong, J.-S., Yoo, S.-A., Kim, H.-S., Kim, H. A., Yea, K., Ryu, S.-H., Chung, Y.-J., Cho, C.-S., and Kim, W.-U. (2010). Inhibition of synovial hyperplasia, rheumatoid t cell activation, and experimental arthritis in mice by sulforaphane, a naturally occurring isothiocyanate. Arthritis & Rheumatism, 62(1):159-170."

Arthritis: Synergistic Effect of Resveratrol and Curcumun on Inflammation

Title: Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of interleukin-1beta-induced nuclear factor-kappab-mediated inflammation and apoptosis.

Summary: We propose that combining these natural compounds may be a useful strategy in OA therapy as compared to separate treatment with each individual compound.

Csaki, C., Mobasheri, A., and Shakibaei, M. (2009). Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of interleukin-1beta-induced nuclear factor-kappab-mediated inflammation and apoptosis. Arthritis Research & Therapy, 11(6):R165+. http://www.citeulike.org/user/HEIRS/article/6067528

Obesity Alone Does Not Cause Arthritis In Animals, Scientists

Obesity Alone Does Not Cause Arthritis In Animals, Scientists Find

ScienceDaily (2009-09-29) -- The link between obesity and osteoarthritis may be more than just the wear and tear on the skeleton caused by added weight. A new study has found that the absence of the appetite hormone leptin can determine whether obese mice experience arthritis, no matter how heavy they are. ... > read full article

The treatment of established murine collagen-induced arthritis with a TNFR1-selective antagonistic mutant TNF.

The treatment of established murine collagen-induced arthritis with a TNFR1-selective antagonistic mutant TNF.

See link.