What is Transforming Growth Factor Beta-1 (TGF B-1)
TGF B-1 is involved in maintaining tissue homeostasis. Helps regulate effects on the innate immune system. TGFb1 is an immunosuppressant (although it can up-regulate the immune system in some cases - see below) and is often chronically overexpressed in disease states including cancer, fibrosis and inflammation. It is moderate to extremely high in Chronic Inflammatory Response Syndrome due to water damaged buildings (CIRS).
Prolonged elevations in TGF-beta 1 levels can create conditions where tissue remodeling and autoimmune transformation become more likely. Although Tgf-beta 1 can be elevated in many disease processes, the idea should be to find and deal with the cause of the overactive TGF b-1 rather than simply reducing it from an elevated state to a normalized state.
Details of TGF B-1 and the transforming growth factor β (TGFβ) cytokine superfamily.
The TGFB cytokine superfamily consists of TGFβs, activins, inhibins, Nodal, bone morphogenetic proteins (BMPs), anti-Müllerian hormone (AMH; also known as Müllerian inhibitory factor), as well as growth and differentiation factors (GDF'er), found in all multicellular organisms. TGFβs are involved in many cellular processes, including growth inhibition, cell migration, invasion, epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodeling, and immunosuppression. Although normally dynamically regulated and involved in maintaining tissue homeostasis, TGFβs are often chronically overexpressed in disease states, including cancer, fibrosis, and inflammation, and this excessive TGFβ production drives disease progression by modulating cell growth, migration, or phenotype. The TGFβ signaling pathway has therefore become a popular target for drug development.
As a growth factor, TGF-beta-1 regulates the growth and proliferation of immune and tissue cells. TGF beta-1 is considered an immunosuppressive (anti-inflammatory) agent, but this is not true if you activate TH cells 17 and there is simultaneous conversion of regulatory T cells in tissues into pathogenic T cells. Research shows that it has a role in activating autoimmunity as well as suppressing autoimmunity.TGF-beta, together with IL-6 and IL-21, promotes the development of Th17 cells.Th17 cells have been identified as a distinct lineage from Th1 and Th2 cells and are required for the induction of several autoimmune diseases, including collagen-induced arthritis, experimental autoimmune encephalitis (EAE) and inflammatory bowel disease (IBD) and also for the ability to remove bacterial infections in the intestine and respiratory tract.
It appears that TGF beta-1 is not immunosuppressive if T-reg cells (recognized by their CD4+/CD25+ cell surface markers) are in the normal range. If T-regs are low, TGF-beta 1 can transform them into pathogenic T cells in tissues, as occurs in CIRS cases. This transformation may depend in part on IL-6. The net result is a positive feedback loop in which more TGF-beta is produced.
This TGF beta-1-induced conversion of T-regs in pathogenic T cells has been shown to be reduced by the use of Losartan at a dose of 25 mg twice daily. VIP is also used to lower TGF beta-1.There are also several herbs and supplements that can lower TGF-beta-1.
The use of losartan is contraindicated in some kidney transplant patients. In patients with diabetic nephropathy, angiotensin converting enzyme (ACE) inhibitors reduce blood pressure and the development of nephropathy, but approximately 10 percent of patients experience side effects that cause discontinuation of ACE inhibitor therapy. Losartan is an angiotensin II receptor antagonist that may have similar effects but fewer side effects.However, research has shown that losartan can induce kidney failure.
Prolonged elevations in TGF-beta 1 levels can create conditions where tissue remodeling and autoimmune transformation become more likely.
Search showsthat members of the arginine-glycine-aspartic acid (RGD)-binding integrin receptor subfamily appear to be the primary mediators of latent TGFβ activation in vivo in many states of organ damage that lead to fibrosis.
The TGF-Beta signaling pathway can beput her.
TGF Beta-1 Actions
- Elevated TGF beta-1 with low CD4+CD25+ cells boosts the production of antibodies against gliadin and cardiolipin. It can also boost the production of other antibodies. You can test these antibodies. If you don't test it, I suggest removing gluten from your diet until you are at least well.
- It inhibits IL-1 and IL-2 dependent T cell proliferation.
- Inhibits activation of helper T cells and cytotoxic T cells.
- It inhibits the secretion of IFN-gamma, TNF-alpha and other interleukins.
- Downregulates the expression of cytokine receptors on activated T cells.
- It inhibits the proliferation of macrophages and monocytes and limits the production of reactive oxygen and nitrogen species.
- Induces Foxp3 expression.
- Necessary for the conversion of Th0 cells to Treg cells in the presence of antigenic stimulation at the appropriate level.
- TGF beta stimulates EGF receptors
- Decreased levels of glutathione will stimulate TGF-β production, and when glutathione is replaced, TGF-β production will be reduced.
High TGF beta-1 results
With high levels of TGF beta-1, you see lung symptoms, neurological problems, learning disabilities, resting tremors, and unusual seizures. (Low and high levels can be linked to autoimmune diseases.) Normal levels keep everything in check. In mice, the lack of TGF beta-1 induces autoimmune diseases.
The common production of autoantibodies most commonly seen in CIRS involves antigliadin antibodies of the IgG class and anticardiolipin antibodies of the IgM class. There are other autoantibodies produced that react to gliadin and cardiolipin. The two listed are the most common and tested by all labs. Others can be tested onCyrex Laboratories.
as a footnote- Low MSH levels are also seen in mold diseases and low MSH is also associated with autoimmunity: 1) Food protein-induced enterocolitis syndrome (FPIES) 2) gliadin autoantibody positivity and 3) True celiac disease is also seen in CIRS (mold disease). These diseases are not antibody diseases. It is a disease with autoantibodies (antibodies against the individual's own proteins).
Lower TGF-B-1 and you will generally get rid of autoimmune issues. Need at normal levels as too low will also induce autoimmunity.
See TGF B-1 in ulcerative colitis inflammatory bowel disease. If TGF b-1 is high, lower TGF b-1 and the inflammatory bowel disease should go away.
High TGF Beta-1 is associated with hair loss (associated with the development of catagen hair - hair follicles that have stopped growing and may be dead, sudden-onset inflammatory response, and high levels of TGF beat-1 can cause damage to the organ of corti causing tinnitus, nystagmus and hearing loss.
TGFb1 affects the kidneys and can cause renal fibrosis.
The reduction of TGFb1 improves neurogenesis and muscle regeneration.
For a list of supplements and herbs that lower TGF b-1, visitTreatment of CIRS.
Treatment of naive T cells with TGFβinduces expression of the forkhead box transcription factor P3 protein (FOXP3), which drives the phenotypic conversion of a naive T cell into a TReg cell conversion of naive CD4 + CD25 peripheral T cells into CD4 + CD25 + TGF regulatory T cells -beta induction of the Foxp3 transcription factor.
Interestingly, suppression of the adaptive immune response induced by TReg cells is also mediated by TGFβ expression. High levels of TGF-beta 1 appear to impair T-cell regulatory function, which normally prevents autoimmune diseases such as those seen in asthma and multiple sclerosis.
High TGF beta-1 is seen in autoimmune diseases as well as regulatory T cells that are very low. This is important in the pathogenesis of autoimmunity. Increased levels of TGF beta-1 will cause regulatory T cells to migrate into tissues to suppress inflammation and suppress autoimmunity. In tissue, if levels of the orphan retinoic acid receptor (ROR) are too low, bad things will happen to our friends, the T reg cells: they turn into pathogenic T cells that produce more TGF beta-1 and produce T - record . The tissue basis for uncontrolled inflammation is an additional burden for CIRS points.
According toDr. shoemaker, the highest levels of TGF beta-1 are seen in the 11-3-52B haplotype, which is hypermobile.
Normal is <2382 pg/mL.
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