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Many thanks, Ohm! Especially interesting I th

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Post# of 154835
(Total Views: 519)
Posted On: 01/03/2025 5:28:31 AM
Posted By: KenChowder
Re: ohm20 #148963
Many thanks, Ohm!

Especially interesting I think is your interest in the involvement of the PAF receptor. The PAFR wasn't on your list, but as you write:

Quote:
I wondered whether PAFR was involved with inducing CCR5 expression or whether CCR5 activated PAFR. Activation of PAFR by its ligand PAF will increase CCR5 expression. But PLA2 (phospholipase A2) is what creates PAF from Lyso-PAF and PLA2 is increased by CCR5. So CCR5 expression in response to bodily insult increases, which increases PLA2, which activates PAF which binds to PAFR which further increases CCR5 resulting in even further increases in inflammatory cytokines. I have not seen that pathway shown anywhere else before but I believe that may be what is happening.



The inflammation/dengue article I was looking through has this to say about the PAFR:

Quote:
A molecule that seems to be a useful as therapeutic target in the context of the dengue is the platelet-activating factor receptor (PAFR). PAF is released from macrophages obtained from patients previously infected with DENV-1 compared with controls.105 Importantly, our group has found a novel role for the PAFR in the pathogenesis of severe dengue.67 Using immunocompetent mice, we found that the course of primary DENV infection was less severe in PAFR−/− mice. Administration of a PAFR antagonist, UK-74,505, after disease manifestation (even 5 days after infection) drastically inhibited the major manifestations of the severe dengue disease, including... lethality.



So if Leron by occupying CCR5 inhibits the pathway that increases PAFR, it does sound like Leron could be useful with dengue fever. And maybe add PAFR to your Regulator List?

The dengue inflammation article I'm referring to is here: https://www.sciencedirect.com/science/article...%20disease.


Again thanks.


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