Tumor Necrosis Factor (TNF-α)

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Tumor Necrosis Factor (TNF-α)

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Tumor Necrosis Factor (TNF-α)
©2020 PFPC

COVID-19
"Early reports have demonstrated severely elevated levels of inflammatory biomarkers and cytokines, including IL-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-2R and ferritin (112)."
(Atri et al., 2020; Qin et al., 2020)

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS - "Dysregulation of immune response in patients with COVID-19 in Wuhan, China" Clin Infect Dis Mar 12:ciaa248 (2020) doi: 10.1093/cid/ciaa248. Epub ahead of print. PMID: 32161940; PMCID: PMC7108125
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108125/
https://www.ncbi.nlm.nih.gov/pmc/articl ... iaa248.pdf

Atri D, Siddiqi HK, Lang J, Nauffal V, Morrow DA, Bohula EA - "COVID-19 for the Cardiologist: A Current Review of the Virology, Clinical Epidemiology, Cardiac and Other Clinical Manifestations and Potential Therapeutic Strategies" JACC Basic Transl Sci Apr 10 (2020) doi: 10.1016/j.jacbts.2020.04.002. Epub ahead of print. PMID: 32292848; PMCID: PMC7151394.
https://www.ncbi.nlm.nih.gov/pmc/articl ... f/main.pdf

Fluoride

Fluoride has long been known to influence TNF activity in various organs of animals and humans (Lu et al., 2017; Sana et al., 2017; Afolabi et al., 2013; Guo et al., 2017).

"... interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05)."


(Afolabi et al., 2003)

Afolabi OK, Oyewo EB, Adekunle AS, Adedosu OT, Adedeji AL - "Oxidative indices correlate with dyslipidemia and pro-inflammatory cytokine levels in fluoride-exposed rats" Arh Hig Rada Toksikol 64(4):521-9 (2013) doi: 10.2478/10004-1254-64-2013-2351. PMID: 24384758.

Guo H, Kuang P, Luo Q, Cui H, Deng H, Liu H, Lu Y, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Effects of sodium fluoride on blood cellular and humoral immunity in mice" Oncotarget 8(49):85504-85515 (2017) doi: 10.18632/oncotarget.20198. PMID: 29156736; PMCID: PMC5689626.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689626/

Lu Y, Luo Q, Cui H, Deng H, Kuang P, Liu H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Sodium fluoride causes oxidative stress and apoptosis in the mouse liver" Aging (Albany NY) 9(6):1623-1639 (2017) doi: 10.18632/aging.101257. PMID: 28657544; PMCID: PMC5509460.

Pereira AG, Chiba FY, de Lima Coutinho Mattera MS, Pereira RF, de Cássia Alves Nunes R, Tsosura TVS, Okamoto R, Sumida DH - "Effects of fluoride on insulin signaling and bone metabolism in ovariectomized rats" J Trace Elem Med Biol 39:140-146 (2017)
https://pubmed.ncbi.nlm.nih.gov/27908407/

Sana S, Ghosh S, Das N, Sarkar S, Mandal AK - "Vesicular melatonin efficiently downregulates sodium fluoride-induced rat hepato- and broncho-TNF-α, TGF-β expressions, and associated oxidative injury: a comparative study of liposomal and nanoencapsulated forms" Int J Nanomedicine 12:4059-4071(2017) doi: 10.2147/IJN.S12411
bmed.ncbi.nlm.nih.gov/28603418/

Gq/11

ALSO: Gq/11 activates MAPK, which in turn regulates TNF-alpha.

"Among the MAPKs, p38 MAPK regulates the expression of tumor necrosis factor- (TNF-) α, interferon- (IFN-) γ, and other cytokines via transcriptional and posttranscriptional mechanisms...Solid evidence has supported that endothelin-dependent ERK/MAPK activation depends on the GqPCR/PLC-β/Ca2+/Src signaling cascade [64]. Taken together, these studies have shown that GqPCR and Gαq are involved in the activation of ERK."

(Zhang & Shi, 2016)

Zhang Lu, Shi Guixiu - "Gq-Coupled Receptors in Autoimmunity" Journal of Immunology Research (2016)
https://www.hindawi.com/journals/jir/2016/3969023/
https://doi.org/10.1155/2016/3969023

"Moreover, IL-17A and TNF-α in PSO patients were negatively associated with the Gαq expression."

(Qian et al., 2019)

Qian H, Wang M, Wang Y, Ying W, Zhang J, Huan Y, He Y, Liu Y, Shi G - "Role of Galphaq in pathogenesis of psoriasis, a new mechanism about the immune regulation in psoriasis" Int Immunopharmacol 68:185-192 (2019) doi: 10.1016/j.intimp.2018.12.054. Epub 2019 Jan 15. PMID: 30654308.
https://pubmed.ncbi.nlm.nih.gov/30654308/

Thyroid

Marchiori RC, Pereira LA, Naujorks AA, Rovaris DL, Meinerz DF, Duarte MM, Rocha JB - "Improvement of blood inflammatory marker levels in patients with hypothyroidism under levothyroxine treatment" BMC Endocr Disord 15:32 (2015) doi: 10.1186/s12902-015-0032-3. PMID: 26100072; PMCID: PMC4476077
https://pubmed.ncbi.nlm.nih.gov/26100072/
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TSH & TNF-alpha

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Wang HC, Dragoo J, Zhou Q, Klein JR- "An intrinsic thyrotropin-mediated pathway of TNF-alpha production by bone marrow cells" Blood 101(1):119-23 (2003) doi: 10.1182/blood-2002-02-0544. Epub 2002 Jun 28. PMID: 12393601
https://pubmed.ncbi.nlm.nih.gov/12393601/

SEE ALSO - BONE: viewtopic.php?f=75&t=2540
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