Thanks for the heads up. I answered him over there
Post# of 153822
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Posted On: 07/05/2022 5:13:52 PM
Thanks for the heads up. I answered him over there.
Quote:
"If we block CCR5 their is still CXCR3 that is driving inflammation."
CCR5 blockade downregulates CX3CL1, CXCL1 and most likely the entire range of CXCR3 ligands in inflammatory conditions. By lowering NF-kb, TNF-a, IFNy and other inflammatory factors it lowers the production of all inflammatory ligands.
"For me, a big marker was the reduction in Interferon Gamma (IFN-y). You see this is not inducible on the CCR5/CCL5 axis. HOWEVER, Interferon Gamma is primarily (maybe exclusively) induced on the CXCR3 connection to its ligands CXCL9, CXCL10, and CXCL11."
Absolutely wrong. IFNy increases expression of both CCR5 and CXCR3 conversely both receptors can ramp up IFNy in a feedback loop. Blocking CCR5 and lowering IFNy should lower CXCR3 expression but I haven't delved into it.
If you look at the triple blocker TAK-779 (CCR2, CCR5 and CXCR3) it really hasn't had success. Block CCR5 you have an immunomodulator. Block to many receptors and you have an immunosuppressant.
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