MediTest
27 Apr 2018
Author
Red
Title

NF-kappaB and inhibitor of apoptosis proteins are required for apoptosis resistance

Comments

Red

Just doing some looking for what might inhibit cIAP-1 / cIAP-2, and I ran across some studies on caffeic acid phenethyl ester (CAPE), a component of bee propolis, which seems to inhibit both cIAP-1 and cIAP-2:

Caffeic acid phenethyl ester-induced PC-3 cell apoptosis is caspase-dependent and mediated through the loss of inhibitors of apoptosis proteins

There have also been some interesting studies on CAPE for inflammation, cancer, and pathogen infection, including one related to Cpn:

Chlamydophila pneumoniae Induces ICAM-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C–Dependent Activation of Nuclear Factor-KB

Interesting in that bee propolis has been used as a folk remedy for some inflammatory disorders... 

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-
Red

Here's a really good paper, complete with very useful diagrams, on this area for anyone interested:

Modulation of Tumor Necrosis Factor by Microbial Pathogens

I personally find this very interesting, but kind of confusing so I did a bit more digging.    From what I understand (and quoting from the above article), previous studies have suggested that Cpn interferes with NF-KappaB regulation via "degradation of BH3-only proteins such as Bim, Puma, Bad, Bik, Bmf, Noxa, and tBid, which inhibit proapoptotic Bax and Bak."

The study at top seems to go one step further and suggests that in Cpn: "Persistent infection resulted in the upregulation of the NF-kappaB regulated inhibitor of apoptosis protein 2 (cIAP-2) but not inhibitor of apoptosis protein 1 (cIAP-1)".  However, the study also suggests "silencing of either cIAP-1 or cIAP-2 sensitized infected cells [or causes apoptosis in other words, I believe] suggesting that IAPs play an important role in the apoptosis resistance of persistently infected cells".

I think I have this correct, but if anyone sees something wrong with this, please let us know... 

 

 

   

 

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Wow Red nice find there. If I get time I'll want to compare this to Zhong's work on CPAF and the BH3-only proteins, and see if it all harmonizes or not. Email me if you want .pdf's of Zhong's papers or something.

Red

 Thanks Eric.   I sent you an e-mail.   I'd love to read Dr Z's study.

Here's another interesting study I just found along these lines.   The intro is very interesting and an easy read: 

Inhibitor of Apoptosis Protein cIAP2 Is Essential for Lipopolysaccharide-Induced Macrophage Survival

This study seems to suggest that LPS stimulates cIAP-2, and interestingly that cIAP-2 deficient mice seem to resist endotoxic shock:

"Proposed mechanism of action: cIAP2–/– mice resist endotoxic shock. LPS challenge of mice causes the activation of multiple types of genes, including the upregulation of the survival genes. The proinflammatory response generates an inherently hostile environment that can be lethal to both pathogen and host immune cell. Therefore, expression of prosurvival genes is probably vital to maintain macrophage viability during an immune response. The inability to upregulate cIAP2 renders LPS-activated macrophages highly susceptible to apoptotic triggers, thereby quickly eliminating the resident macrophage population soon after the initiation of a systemic inflammatory response. This leads to the loss of the principal source of proinflammatory cytokines and subsequently to the attenuation of the immune response, preventing the development of multiple organ failure."

 

 

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-
Red

Interesting study on Vitamin D3 along these lines:

Apoptosis Induction by 1,25-Dihydroxyvitamin D3 in Prostate Cancer

"VD3 induced decreases in levels of antiapoptotic proteins Bcl-2, Bcl-XL, and Mcl-1, BAG1L, XIAP, cIAP1, and cIAP2 (without altering proapoptotic Bax and Bak) in association with increases in apoptosis"

 

 

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-
Red

Thanks again Eric.   Just sent you a message.  It should be in your inbox...

 

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-
Red

After reading a recent news article on Resveratrol, finding it interesting for its effects on heart disease and other inflammatory diseases, and thinking that it must have some effect on Cpn, I did some digging into its potential anti-Cpn effects.   I found one study about it in cpnhelp:

http://www.cpnhelp.org/?q=resveratrol_and_curcumin_

But I found an article about another interesting study that suggest that Resveratrol might be anti-chlamydial via its effects on NF-Kappa B:

http://intranet.ag.ohio-state.edu/~news/story.php?id=2791

And more specifically, another study suggests to me that it may be anti-Cpn via its ability to potentiate the "SIRT1 protein on the cIAP-2 promoter region, an effect that correlates with a loss of NF-κB-regulated gene expression and sensitization of cells to TNFα-induced apoptosis":

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=423286 

See the studies above for more info on Cpn, NF-Kappa B and cIAP-2.

 
Interesting...

 

 

On Combined Antibiotic Protocol for Cpn in Rosacea since 01/06

Treatment for Rosacea

  • CAP:  01/06-07/07
  • High-Dose Vit D3, NAC:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Thanks Red. This is really fascinating and I appreciate the links. I didn't know anything about Resveratrol. I missed the first link. Now I really want to know more. Wine drinkers on this site will find this particularly useful and interesting, especially about the New York wines. I haven't had much wine since I started the protocol because of the meds, but maybe those who have a glass more often have also reaped some of the anti-Cpn benefits.

CAP 2/14/06 for Cpn-CFS/FM/CD

Red