Inflammation & Sensitivity of Skin

Inflammation

Inflammation is important because it is a response that is used to protect the body, but there are problems associated with inflammation when it becomes excessive.

SNPs in the Tumor Necrosis Factor-Alpha 1 (Tnfa-1) gene and Microsomal Epoxide Hydrolase (EPHX) gene can cause conditions that promote Inflammation and sensitivity. For example, excessive Tnfa-1 signaling of inflammation proteins called cytokines can take your body from a natural protecting mechanism to a harmful one that attacks itself. Inflammation is a response from your body to protect you from foreign substances, but when it becomes excessive and can’t be switched off, it can cause premature skin aging.

The buildup of foreign substances from environmental pollution can be a serious issue if you have a SNP that prevents you from detoxifying. An accumulation of these toxic substances occurs because the lack of the enzyme that breaks them down. A defective gene causes it. If you cannot detoxify these foreign substances, damaging epoxides accumulate and cause sensitivity along with the release of inflammatory cytokines. These cytokines then cause free radical damage, which can lead to oxidation.

Dysfunction

Tnfa sends a signal to your immune cells to defend your body. Dysfunction occurs when Tnfa-1 signaling becomes over-reactive, causing a long-term issue that can harm the skin, tissue and organs. Pollutants accumulate due to a defect in the EPHX1 gene that causes a buildup of foreign chemicals (epoxides) your body doesn’t recognize, so it will signal inflammatory proteins that will attack these foreign chemicals relentlessly. A long-term signaling of the damaging inflammatory markers will be caused by these situations. Allergies and heightened sensitivities to pollutants and chemicals prevail as a consequence of this long-term over-signaling, which furthers inflammation.

Optimal functioning

Tnfa sends a signal to your immune cells to defend your body. When your body is functioning optimally, there is non-excessive signaling of Tnfa creating a short-term response to deal with the body’s crisis. You are exposed to foreign chemicals such as pesticides and cigarette smoke and the EPHX1 enzyme is activated to break down the molecules of these chemicals safely and detoxify them. There is no accumulation of these chemicals and their toxic byproducts, therefore no long-term release of inflammatory cytokines is present.

Symptoms include:

• Itching and redness
• Rashes and swelling
• Chemical and environmental sensitivity (i.e., skin sensitive to cold or heat)

Supplements:

• Hepato DPO
• Onco Defense
• Green Tea Extract
• ALAmed CR
• Curcumin Cream (available at Medical Detective store)
• Phosphaline
• Curcuminoid CR
• Curcuminoid BCM-95
• Arctic Omega 900
• Arctic Omega Krill
• E-ssential
• Saloxicin (available at Medical Detective store)
• CollaGENerate
• Synovial Active
• Acetyl GSH
• Circuvasc

Tnfa-1

Tnfa is a cytokine, which is a signaling molecule for immune cells. Tnfa sends a signal and inflammatory proteins are released to stop the present perceived threat or attack to the body to keep it from being damaged. Inflammation is supposed to be a healthy response to trauma, infection, chemicals, viruses, pollution, allergens, cuts and wounds. Inflammation occurs when Tnfa sends a signal to your immune cells to defend your body. With a healthy response (no genetic variation in Tfna), proper signaling of Tfna is a short-term response. With a mutation in this gene, the signaling becomes over-reactive, causing a long-term issue that can harm the tissue and organs. Symptoms can include skin issues such as dermatitis, eczema and erythera. Allergies and heightened sensitivities to pollutants and chemicals prevail as a consequence of this long-term over- signaling. Those with a gene mutation and insulin resistance have excessive signaling from the Tnfa.

Accumulation of the cytokine Tnfa-1 induces prolonged and excessive inflammation. If you have a SNP in this gene, you will have an issue with turning off this chemical messenger cytokine and the cytokine will build up in your body, affecting everything. Not only does it play a role in skin, but also the bowel, joints, brain, and heart. [1,2,3]

Those that have this SNP will have issues such as asthma, psoriasis, skin rashes and acne. [3, 4, 5]

Tnfa-1 is a cytokine (inflammatory marker—a chemical messenger for the body’s immune system that mobilizes white blood cells to defend against invaders or fight infections. Tnfa-1 mediates acute and chronic inflammation, anti-tumor responses, and infection. It is about balance when it comes to activating inflammatory responses. For example, if you did not have a high risk in this category (genetic defect in Tnfa-1 and you treat your skin as if you did by using anti-inflammatory cosmetics or supplements, you could make an already balanced Tnfa-1 underbalanced. You activate something called DUOX1-derived H2o2 and NFKB, which can cause skin lesions of psoriasis and lichen planus.

“Depletion of Tnfa or its receptor Tnfr2 caused skin inflammation and hyper-proliferation of keratinocytes through the activation of Duox1/H2O2/NF-kB positive inflammatory loop.”[1]

Tnfa binds two receptors together and they have opposing tasks. One of the receptors, TnfR1, causes cell death. The second receptor, TnfaR2, signals the pathway for cell survival instead of cell death.

Epoxide Hydrolase (EPHX)

What if you have a SNP that predisposes you to poor detoxification of environmental pollutants and xenobiotics? This causes sensitivity to everyday toxins we come into contact with and can cause an inflammation response in the skin and the body if the body cannot successfully detox the chemicals. [6]

The body must be able to detox xenobiotics and other environmental pollutant factors. When you have a SNP in the gene that detoxes, you will get inflammation, making you sensitive to these pollutants. With this problem comes skin aging. One of the most important contributing factors of skin aging as is UV irradiation. [7] Toxins and UV light are also potent inducers of TNF-α release from keratinocytes. [8]

Epoxide Hydrolase (EPHX) is a phase I metabolizing enzyme that detoxifies epoxides. Epoxides come from xenobiotics (chemical foreign substances found in body that aren’t naturally found in body). They come from external sources of environmental pollutants such as pesticides, smoke from cigarettes, antibiotics, food additives, and carcinogenic substances such as BPA found in lining of cans and in plastic (i.e., plastic water bottles). [9]

“The term xenobiotic is derived from the Greek words ξένος (xenos) = foreigner, stranger and βίος (bios, vios) = life, plus the Greek suffix for adjectives -τικός, -ή, -ό (tic).” [10]

They are highly reactive chemicals that can cause cancers.

If you have a SNP in EPHX enzyme, it is important to increase it so there isn’t an accumulation of epoxides. You do this by finding ways to detoxify properly and increasing the liver’s strength. A sluggish liver because of this gene SNP and/or toxic overload can cause premature aging and skin conditions.

Need antioxidants to fight free radicals induced by chronic inflammation because of genetic defect predisposition in TNFA1?

Resources:

*http://backinpowerinc.com/six-anti-aging-genes-and-solutions-for-your-skin/

1. Candel S, de Oliveira S, López-Muñoz A, García-Moreno D, Espín-Palazón R, Tyrkalska SD, et al. (2014) Tnfa Signaling Through Tnfr2 Protects Skin Against Oxidative Stress–Induced Inflammation. PLoS Biol 12(5): e1001855. doi:10.1371/journal.pbio.1001855
2. Alvarez V et al. Association between the TNFalpha-308 A/G polymorphism and the onset-age of Alzheimer disease. Am J Med Genet. 2002;114(5):574-7.
3. Elahi MM et al. A variant of position -308 of the Tumour necrosis factor alpha gene promoter and the risk of coronary heart disease. Heart Lung Circ. 2007 Jun 18;
4. Baz K. Association between tumor necrosis factor-alpha gene promoter polymorphism at position -308 and acne in Turkish patients. Arch Dermatol Res. 2008. 300(7):371-6.
5. Witte JS et al. Relation between tumour necrosis factor polymorphism TNFalpha-308 and risk of asthma. Eur J Hum Genet. 2002;10(1):82-5.
6. Morisseau C and BD Hammock. Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles. Annu Rev Pharmacol Toxicol. 2005;45:311-33
7. Oxidative stress in aging human skin. http://dx.doi.org/10.3390/biom5020545. 2015, 5(2) 545-589
8. Steinhoff M. and Luger T.A. The Skin Cytokine Network. In: Skin Immune System: Cutaneous Immunlogy and Clinical Immundermatology. Editor: Boss J.D. 2004. Boca Raton, FL. CRC Press. P. 353
9. O’Neill V.A., et al. Epoxide hydrolase activity in human skin. British Journal of Clinical Pharmacology. 1981. 12:517-521
10. https://en.wikipedia.org/wiki/Xenobiotic