TGF B-1

Transforming Growth Factor Beta-1(TGF B-1)

This page contains educational material about Chronic Inflammatory Response Syndrome due to water damaged building (CIRS). This is a biotoxin illness is that is caused by mold. Other biotoxin illnesses have similar signs and symptoms. They are also treated similarly. Some of them are discussed on this site. This information is for educational purposes only. Nothing in this text is intended to serve as medical advice. All medical decisions should be made only with the guidance of your own personal medical authority. I am doing my best to get this data up quickly and correctly. If you find errors in this data, please let me know.

Biotoxin/Mold

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Transforming Growth Factor Beta-1(TGF B-1)

TGF B-1 is involved in maintenance of tissue homeostasis. It helps regulate effects in the innate immune system. TGFb1 is an immune suppressor (although can upregulate the immune system in some instances - see below) and is often chronically over-expressed in disease states, including cancer, fibrosis and inflammation. It is moderately to extrememly high in Chronic Inflammatory Response Syndrome due to water-damaged building (CIRS).

Prolonged elevations of TGF-beta 1 levels can create conditions where tissue remodeling and autoimmune transformation become more likely.

More Details on TGF B-1 and the transforming growth factor-β (TGFβ) superfamily of cytokines.

The TGFB superfamily of cytokines consists of TGFβs, activins, inhibins, Nodal, bone morphogenetic proteins (BMPs), anti-Müllerian hormone (AMH; also known as Müllerian-inhibiting factor) as well as growth and differentiation factors (GDFs), is found in all multicellular organisms. The TGFβs are involved in many cellular processes, including growth inhibition, cell migration, invasion, epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) remodelling and immune-suppression. However, although normally dynamically regulated and involved in maintenance of tissue homeostasis, TGFβs are often chronically over-expressed in disease states, including cancer, fibrosis and inflammation, and this excessive production of TGFβ drives disease progression by modulating cell growth, migration or phenotype. The TGFβ signalling pathway has therefore become a popular target for drug development.

As a growth factor, TGF-beta-1 regulates immune and tissue cell growth and proliferation. TGF beta-1 is thought of as an immune suppressant (anti-inflammatory) but this is not true if you are turning on TH 17 cells and there is conversion of T regulatory cells in tissue to pathogenic T cells at the same time. Research shows it has a role in activation of autoimmunity as well as supressing autoimmunity. TGF-beta, together with IL-6 and IL-21, promotes Th17 cell development. Th17 cells have been identified as a lineage distinct from Th1 and Th2 cells, and are required for induction of several autoimmune diseases, including collagen-induced arthritis, experimental autoimmune encephalitis (EAE), and inflammatory bowel disease (IBD), and also for the ability to clear bacterial infections of the intestine and the airways.

It apperas TGF-beta 1 is not immune suppressive if T-reg cells (known by their CD4+/CD25+ cell surface markers) are in normal range. If T-regs are low, TGF- beta 1 can transform them into pathogenic T-cells in tissues, as happens 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 gets produced.

This TGF-beta 1-induced conversion of T-regs into pathogenic T cells can be reduced using Losartan at a dose of 25 mg twice daily. VIP is also used to lower TGF beta-1. There are additionally herbs and supplements that can reduce TGF-beta-1.

Use of losartan is CI in renal transplant patients. In patients with diabetic nephropathy, angiotensin-converting–enzyme (ACE) inhibitors reduce blood pressure and the progression of nephropathy but approximately 10 percent of patients have side effects that cause the discontinuation of ACE-inhibitor therapy. Losartan is an angiotensin II–receptor antagonist that may have similar efficacy but fewer side effects. However, research has shown losartan may induce renal insufficiency.

Prolonged elevations of TGF-beta 1 levels can create conditions where tissue remodeling and autoimmune transformation become more likely.

The TGF-Beta Signaling Pathway can be viewed here.

TGF beta-1 Actions

Elevated TGF beta-1 with low CD4+CD25+ cells drives production of antibodies to gliadin and cardiolipin. It may drive production of other antibodies also. You can test for these atnibodies. If you don't test I suggest removing gluten from your diet until you are well at least.

Inhibits IL-1 and IL-2 dependent T cell proliferation.

Inhiibits activation of both T helper and cytotoxic T cells.

Inhibits secretion of IFN-gamma, TNF-alpha and other interleukins.

Downregulates the expression of cytokine receptors on activated T cells.

Inhibits the proliferation of macrophages and monocytes and limits their production of reactive oxygen and nitrogen species.

Induces Foxp3 expresion.

Necessary for the conversion of Th0 cells to Treg cells in the presence of antigen stimulation of the appropriate level.

TGF beta stimulates EGF receptors

Results of high TGF beta-1

With high levels of TGF beta-1 you see lung symptoms, neurological problems, autoimmiune disease, learning disability, MS, TM , resting tremors, unusual seizures.

The common autoantibody production most commonly seen with CIRS involves antigliadin antibodies of the IgG class and anticardiolipins of the IgM class. There are other autoantibodies made that react to gliadin and cardiolipin. The two listed are the most common.

MSH deficiency-associated 1) Food protein-induced enterocolitis syndrome (FPIES) 2) Gliadin autoantibody positivity and 3) True celiac disease are seen with CIRS These illnesses are not antibody illness. These are an autoantibody illness.

Lower TGF-B-1 and you get rid of the autoimmune problems usually.

Look at TGF B-1 in ulcerative colitis inflammatory bowel diseases. If TGF b-1 is high, lower the TGF b-1 and the inflammatory bowel diseases should disappear.

High TGF Beta-1 is associated with loss of hair (associated with development of catigen hairs – hair follicules that have stopped growing and actually may be dead, sudden onset of inflammatory response and high levels of TGF beat-1 can cause injury to the organ of corti causing tinnitus, nystagmus, and hearing loss.

TGFb1 impacts the kidneys and can create renal fibrosis.

Lowering TGFb1 enhances neurogenesis and muscle regeneration.

For a list of supplements and herbs that lower TGF b-1 please go to Treatment of CIRS.

TGFβ mediates the immunosuppressive differentiation of T cells - The polarization of immune cells in the tumour environment by TGF beta.
Flavell RA, Sanjabi S, Wrzesinski SH, Licona-Limón P
Nat Rev Immunol. 2010 Aug; 10(8):554-67.
[PubMed]

Treatment of naive T cells with TGFβ induces the expression of the transcription factor forkhead box protein P3 (FOXP3), which drives the phenotypical conversion of a naive T cell to a TReg cell-Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3.
Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM
J Exp Med. 2003 Dec 15; 198(12):1875-86.
[PubMed] & Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer.
Tone Y, Furuuchi K, Kojima Y, Tykocinski ML, Greene MI, Tone M
Nat Immunol. 2008 Feb; 9(2):194-202.
[PubMed]

Interestingly, TReg cell-induced suppression of the adaptive immune response is also mediated through the expression of TGFβ. The high levels of TGF-beta 1 appear to damage T-regulatory cell function that usually prevent autoimmune conditions such as seen in asthma and multiple sclerosis.

SEE 109. Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science. 1994;265:1237–1240. [PubMed]
110. Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nature Rev Immunol. 2008;8:523–532. [PMC free article] [PubMed]
111. von Boehmer H, Daniel C. Therapeutic opportunities for manipulating TReg cells in autoimmunity and cancer. Nature Rev Drug Discov. 2013;12:51–63. [PubMed]

High TGF beta-1 is seen in autoimmiune illness as well as T-regulatory cells that are too low. This is important in pathogenesis of autoimmunity. Rising levels of TGF beta-1 will cause the migration of t-regulatory cells into tissue to suppress inflammation and suppress autoimmunity. In the tissue if the levels of the retinoic acid orphan receptor (ROR) are too low bad things will happen to our friends the T reg cells: they are converted to pathogenic T cells that make more TGF beta-1 and low T regs. The tissue basis of uncontrolled inflammation is an additional burden for CIRS pts.
Dr. Shoemaker uses low dose Losartan to safely lower TGF beta-1 and the lowered TGF beta -1 was accompanied by resolution of autoimmune defects. (This study had a flaw as they did not have a good T-regulatory cell assay at the time.)

According to Dr Shoemaker, the highest levels of TGF beta-1 are seen in the haplotype 11-3-52B who are hypermobile.

Normal is <2382 pg/ml.

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Biotoxin/Mold