You can read what Wikipedia has to say about Beta catenin
, the Wnt (pronounced Whint) pathway, on which beta catenin is supposed to be acting on, and the PTGER2
, through which the alterations of the cytokine balance is supposed to act, and please write in the comments on the importance you attach to this.
The study suggests a key role in both keeping Tregs functional and regulating the key pro- (Gamma interferon) and anti-inflammatory (interleukin 10) cytokines mentioned above. The study revealed that beta-catenin works together with a protein receptor called PTGER2 to trigger inflammation induced by a high salt intake.
The authors conclude:"Our findings suggest that the beta-catenin-PTGER2 axis serves as a bridge between environmental factors and autoimmune disease by modulating Treg function, and this axis may be involved in the pathogenesis of autoimmune disease."
The clinical implications
"Not only upregulation of [the] pro-inflammatory cytokine IFN-gamma but also downregulation of [the] anti-inflammatory cytokine IL-10 might mark dysfunctional [Tregs] in MS patients."
"Therefore, it would be ideal to work on [both directions]: prevent IFN-gamma and enhance IL-10, it's always important to balance pro- and anti-inflammatory arms together."
But where are we on this?
Prevent gamma interferon on mice and disease gets worse not better, but do it in humans
Skurkovich S, Boiko A, Beliaeva I, Buglak A, Alekseeva T, Smirnova N, Kulakova O, Tchechonin V, Gurova O, Deomina T, Favorova OO, Skurkovic B, Gusev E.Randomized study of antibodies to IFN-gamma and TNF-alpha in secondary progressive multiple sclerosis. Mult Scler. 2001; 7:277-84.I
Patients who received antibodies to IFN-gamma showed statistically significant improvement compared to the placebo group--a significant increase in the number of patients without confirmed disability progression. This was supported by MRI data (a decrease in the number of active lesions) and systemic changes in cytokine status (a decrease in IL-1beta, TNF-alpha, and IFN-gamma concentrations in supernatants of actvated blood cells of these MS patients and an increase in TGF-beta production).
Seems to be correct
However enhance IL-10...I'm not so sure. Mention IL-10 to a T cell immunologist and they think immunoregulation. However it is a B cell growth factor too and so maybe not all good..
Wiki says for IL-10 :"It downregulates the expression of Th1 cytokines, MHC class II antigens, and co-stimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production".
"Contrary to expectations, rHuIL-10 treatment did not significantly impact disease in patients with Crohn's disease.or rheumatoid arthritis. rHuIL-10 treatment failed to achieve clinical significance in a randomized, double blind, placebo controlled Phase II trial in psorisis. Further investigation of rHuIL-10's effects in humans suggests that rather than inhibiting inflammation, rHuIL-10 is capable of exerting pro-inflammatory effects".
tsF were immortalised fibroblasts that were transfected to make IL-10 (IL-10.tsF2). Tsf2 and Tsf4 were different cell lines
So the response to therapy can say a lot about the putative mechanisms on which they are based
In my opinion targeting cytokines is not a good approach, as cytokines exist in balances. Inhibit one and another goes up to compensate and vice versa. You say beta interferon and I say, yep point proven not the best approach.
Anyway have a read and make a comment for the readers