Tnf-a Implicated In Pge2 Vs. Pgd2 Production Ratios In Murine Macrophages

[Gone]

https://www.ncbi.nlm.nih.gov/m/pubmed/9388257/

http://www.jbc.org/content/272/49/31065.full.pdf

"In response to zymosan, TNFalpha specifically induced a 5-fold increase in PGE2 synthesis, at the same time decreasing PGD2 production in a reciprocal fashion"

This is from 1997, we learned about PGD2 in 2012.

I understand that this study takes place in mice, and that hair follicles were not the focus of the study. But...

This might be important.

 

[Folliman]

Relevant https://www.ncbi.nlm.nih.gov/pubmed/1981213

 

[Gone]

Relevant, but in the mouse example Tnf-a had a positive effect on Pge2 and a negative effect on Pgd2, which would be the opposite effect a drug like Sulfasalazine has in this example.

 

[Gone]

https://books.google.com/books?id=3...HWXwDa0Q6AEIDTAB#v=onepage&q=tnfa dht&f=false

"DHT also inhibited the effects of TNFa on the cells overexpressed with AR, indicating that sufficient expression level of functional AR was necessary for the inhibitory effect on TNFa."

DHT can affect TNFa. TNFa can regulate PGD2 and PGE2 ratios.

 

[Folliman]

The problem is sulfasalazine is known for increasing PGE2 and reducing PGD2. See the dilemma?

 

[Gone]

Do you have a source

 

[Folliman]

https://www.ncbi.nlm.nih.gov/pubmed/14706679

http://rsx.sagepub.com/content/11/1/22.full.pdf+html

 

[Gone]

I'm a lot more familiar with the concepts we're dealing with now. Sulfasalazine is a PDGH inhibitor. PDGH is what metabolizes/breaks down PDE2. So, Sulfasalazine, along with other drugs that inhibit PDGH, increase (double) PGE2 because they prevent its breakdown.

http://science.sciencemag.org/content/348/6240/aaa2340

It's not necessarily a contradiction that Sulfasalazine (a TNFa inhibitor) and TNFa itsef, could increase PGE2, TNFa just has a stronger effect. Furthermore, what's important is that TNFa Inversely regulates PGD2 and PGE2, which is a superfactor in baldness, most people use PGD2 inhibitors and PGE2 seperately. Sulfasalazine, while it doubles PGE2, also increases PGD2.

"Prostaglandins PGD2 and PGF2a are also candidate substrates of 15-PGDH. Basal PGD2 levels were lower than PGE2 levels in all four mouse tissues examined, and showed a lesser, though still significant, induction with SW033291" [a PDGH inhibitor]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481126/#SD1

 

[Folliman]

I see, this is interesting. So it would be very beneficial for hair to inhibit PGDH while increasing TNFa, assuming we humans respond as mice of course. I'll look more into this.

 

[Gone]

Yeah I thought it was interesting too. I think it's likely that Tnf-a will affect both pgd2 and pge2 in humans, but the effect it has could be totally or in-significant based on the degree to which it changes the ratios. If it is indeed standard that balding scalps contain 12 times as much pgd2, and half as much pge2, and tnf-a expresses that role in balding people, then we have a culprit, for at least the progression of baldness.

I think it's so sinister that the body considers the bald phenotype, the appearance of being bald, to be worth going through every avenue to make it so. It's truly like an evolving beast that needs every single mode of attack to take down. At least we have androgens figured out.

 

[Folliman]

Sinister indeed, my friend. I can't wait for CRTH2 blockers to hit the market, fevipiprant being the first one in 2019. Trying to work my way around it in the meantime. I would try sulfa, but I'm allergic. :/