NF-kappa B

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.

NF-kappa B

Postby admin » Sun May 17, 2020 9:50 am

NF-kappa B
© 2020 PFPC

COVID-19

"The NF-κB pathway is often targeted by viral pathogens to enhance viral replication, host cell survival and host immune evasion. Viruses may activate or suppress NF-kB. (5). There have many studies on SARS-COV since 2002-2003 SARS epidemic. SARS-COV2 (COVID-19) belongs to the same family of corona viruses and shares many similarities (3)...
COVID 19 activates NF-kB pathway, like MERS and SARS-COV (3). SARS-COV virus has been studied in vitro and in mice and was shown to promote inflammatory mediators in vitro and in vivo through actions on NF-kB. Levels of NF-kB were higher in lungs of (recombinant SARS (rSARS)-infected mice. Inhibitors of NF-kB improved survival of BALB/c mice and reduced rSARS-COV-induced inflammation, without influencing viral titers (6) . NF-kB is specifically induced by SARS-COV S protein to produce inflammatory mediators that are associated with ARDS in SARS in vitro (7)."


COVID-19 increases NF-kappaB levels.
https://www.bmj.com/content/368/bmj.m1252/rr-1

Wu YH, Chiu DT, Lin HR, Tang HY, Cheng ML, Ho HY - "Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through
Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling" Viruses 7(12):6689-706 (2015) doi: 10.3390/v7122966.

Martínez-Sánchez G, Schwartz A, Donna VD - "Potential Cytoprotective Activity of Ozone Therapy in SARS-CoV-2/COVID-19" Antioxidants (Basel) 9(5):E389 (2020)
doi: 10.3390/antiox9050389. PMID: 32384798.
https://pubmed.ncbi.nlm.nih.gov/32384798/

Fluoride

"The use of sodium fluoride (NaF) as a major ingredient for tooth paste, mouth wash, and mouth rinse has become inevitable in our day-to-day life.....Immunohistochemistry revealed that NaF caused increase expressions of Kidney injury marker 1 (Kim-1), nuclear factor kappa bet (NF-κB), nuclear factor erythroid 2-related factors 2 (Nrf2), and cardiac troponin I (CTnI)."

(Oyagbemi et al, 2018)

Oyagbemi AA, Omobowale TO, Ola-Davies OE, Asenuga ER, Ajibade TO, Adejumobi OA, Afolabi JM, Ogunpolu BS, Falayi OO, Saba AB, Adedapo AA, Yakubu MA - "Luteolin-mediated Kim-1/NF-kB/Nrf2 signaling pathways protects sodium fluoride-induced hypertension and cardiovascular complications" Biofactors 44(6):518-531 (2018)
doi: 10.1002/biof.1449. Epub 2018 Nov 26. PMID: 30474894.
https://pubmed.ncbi.nlm.nih.gov/30474894/

Luo Q, Cui H, Deng H, Kuang P, Liu H, Lu Y, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Sodium fluoride induces renal inflammatory responses by activating NF-κB signaling pathway and reducing anti-inflammatory cytokine expression in mice" Oncotarget 8(46):80192-80207 (2017) doi: 10.18632/oncotarget.19006. PMID: 29113295; PMCID: PMC5655190.
https://pubmed.ncbi.nlm.nih.gov/29113295/

Chen L, Kuang P, Liu H, Wei Q, Cui H, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Sodium Fluoride (NaF) Induces Inflammatory Responses Via Activating MAPKs/NF-κB Signaling Pathway and Reducing Anti-inflammatory Cytokine Expression in the Mouse Liver" Biol Trace Elem Res 189(1):157-171 (2019) doi: 10.1007/s12011-018-1458-z PMID: 30062462
https://pubmed.ncbi.nlm.nih.gov/30062462/

Refsnes M, Skuland T, Låg M, Schwarze PE, Øvrevik J - "Differential NF-κB and MAPK activation underlies fluoride- and TPA-mediated CXCL8 (IL-8) induction in lung epithelial cells" J Inflamm Res 7:169-85 (2014)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270361/

G q/11

NF-Kappa B is downstream from Gq/11 activation.

"Endothelial cells can sense different flow patterns and convert the mechanical signal of laminar flow into atheroprotective signals, including eNOS activation, whereas disturbed flow in atheroprone areas induces inflammatory signaling, including NF-κB activation. How endothelial cells distinguish different flow patterns is poorly understood. Here we show that both laminar and disturbed flow activate the same initial pathway involving the mechanosensitive cation channel Piezo1, the purinergic P2Y2 receptor, and Gq/G11-mediated signaling. However, only disturbed flow leads to Piezo1- and Gq/G11-mediated integrin activation resulting in focal adhesion kinase-dependent NF-κB activation."


(Albarrán-Juárez et al., 2018)

Albarrán-Juárez J, Iring A, Wang S, Joseph S, Grimm M, Strilic B, Wettschureck N, Althoff TF, Offermanns S - "Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation" J Exp Med 215(10):2655-2672 (2018) doi: 10.1084/jem.20180483. Epub 2018 Sep 7. PMID: 30194266; PMCID: PMC6170174.

Meng Y, Yu CH, Li W, Li T, Luo W, Huang S, Wu PS, Cai SX, Li X - "Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway" Am J Respir Cell Mol Biol 50(4):723-36 (2014) doi: 10.1165/rcmb.2012-0451OC. PMID: 24168260.
https://pubmed.ncbi.nlm.nih.gov/24168260/

NOTE: AT1 increases, Aniotensin (1-7)/Mas inhibits.

SEE ALSO: ERK/MAPK viewtopic.php?f=66&t=1914
Tumor Necrosis Factor: viewtopic.php?f=66&t=1895

Thyroid

"THs induced nongenomically the rapid translocation of protein kinase C (PKC) ζ isoform to cell membranes, extracellular-signal-regulated kinases (ERK1/2) phosphorylation and nuclear factor-κB (NF-κB) activation. The signaling cascade include sphingomyelinases acting up-stream the activation of PKCζ isoform, while ERK and NF-κB are activated downstream this PKC isoenzyme."


Barreiro Arcos ML, Sterle HA, Paulazo MA, Valli E, Klecha AJ, Isse B, Pellizas CG, Farias RN, Cremaschi GA - "Cooperative nongenomic and genomic actions on thyroid hormone mediated-modulation of T cell proliferation involve up-regulation of thyroid hormone receptor and inducible nitric oxide synthase expression" J Cell Physiol 226(12):3208-18 (2011) doi: 10.1002/jcp.22681. PMID: 21344381.
https://onlinelibrary.wiley.com/doi/abs ... /jcp.22681

"In thyroid, NF-κB signaling is crucial for thyrocytes survival and expression of critical thyroid markers, including Nis, Ttf1, Pax8, Tpo, and thyroglobulin, making this transcription factor essential for maintenance of normal thyroid function."


(Reale et al., 2018)

Reale C, Zotti T, Scudiero I, Vito P, Stilo R - "The NF-κB Family of Transcription Factors and Its Role in Thyroid Physiology" Vitam Horm 106:195-210 (2018) doi: 10.1016/bs.vh.2017.05.003. Epub 2017 Sep 4. PMID: 29407436.
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