Nuclear receptors and ligands

Nuclear receptors are a class of proteins found within the interior of cells that are responsible for sensing the presence of hormones and certain other molecules. A unique property of nuclear receptors which differentiate them from other classes of receptors is their ability to directly interact with and control the expression of genomic DNA.

Some of the molecules (or ligands) which bind the nuclear receptor activate (agonize) it and some inactivate (antagonize) it.

It is commonly accepted that most ligands, approximately 95% to 98%, inactivate the nuclear receptors. Since the nuclear receptors play a significant role in the immune response, this factor alone may explain why so many drugs and substances found in food and drink are immunosuppressive.

Transcription of antimicrobial peptides

One of the VDR's key functions is the transcription of naturally produced broad-spectrum antibacterials which target pathogens.1) 2)


Telmisartan, an ARB, is an extreme immunosuppressant by means of being a strongly active antagonist of VDRs

My in-silico work showed Telmisartan totally shuts off the VDR and is therefore highly immunosuppressive.

Trevor Marshall, PhD (personal communication to research team)

Due to differences in molecular structure, each ARB is shown to have significantly different properties when interacting with the nuclear receptors in the immune cells. For example: where Telmisartan will quickly and completely suppress immune function, frequent dosing of olmesartan medoxomil (which is an agonist of VDRs) over a prolonged period allows recovery of immune function via activation of the vitamin D receptor.

Particular care

Patients seeking to keep the health regained by following the Marshall Protocol, must take care, even when apparently recovered, or having achieved resolution of many or most of their troublesome symptoms, to diligently avoid challenge to their longterm status, by continuing to avoid immuno-suppressants, and by asking the support team for information if any doctor recommends an alternative regime. Many standard treatment for auto-immune symptoms are based solely on suppressing the immune response. That is to say, the patient will shortly feel and look much better, but long term health again becomes compromised as bacteria, viruses and fungi use whatever means available to re-invade.


===== Notes and comments =====

Wang T, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, Tavera-Mendoza L, Lin R, Hanrahan JW, Mader S, White JH. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004 Sep 1;173(5):2909-12. doi: 10.4049/jimmunol.173.5.2909.
[PMID: 15322146] [DOI: 10.4049/jimmunol.173.5.2909]
Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 2005 Jul;19(9):1067-77. doi: 10.1096/fj.04-3284com.
[PMID: 15985530] [DOI: 10.1096/fj.04-3284com]
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