Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A₃ adenosine receptor in HL-60 cells.

ABSTRACT: The A₃ adenosine receptor (AR) is an important inflammatory and immunological target. However, the underlying mechanisms are not fully understood. Here, we report the gene regulation in HL-60 cells treated acutely with highly selective A₃AR agonist MRS5698, positive allosteric modulator (PAM) LUF6000, or both. Both pro- and anti-inflammatory genes, such as IL-1a, IL-1β, and NFκBIZ, are significantly upregulated. During our observations, LUF6000 alone produced a lesser effect, while the MRS5698 + LUF6000 group demonstrated generally greater effects than MRS5698 alone, consistent with allosteric enhancement. The number of genes up- and down-regulated are similar. Pathway analysis highlighted the critical involvement of signaling molecules, including IL-6 and IL-17. Impo

SUBMITTER: Gao ZG 

PROVIDER: S-EPMC11377395 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature