Heteromers Between Chemokine Receptors And Alpha1-Adrenergic Receptors/Vasopressin Receptor 1A As Drug Targets To Modulate Inflammation And Cell Trafficking

Tech ID: 22A093

­Advantaages:

  • Novel therapeutic opportunities for modulating inflammation and cell trafficking
  • Insights into neuroendocrine control of immune cell behavior

Summary: 

 This innovative technology centers around the discovery and characterization of heteromers formed between chemokine receptors (CR) and a1-adrenergic receptors (AR), specifically a1B/D-ARs. Extensive research has revealed the crucial role of these heteromeric complexes in regulating the function of CR heteromerization partners. Leveraging cutting-edge CRISPR/Cas9 gene editing, a a1B-AR knockout was successfully developed in THP-1 cells (THP-1_ADRA1BKO), leading to impaired cell migration toward ligands of CR heteromerization partners of a1B/D-AR -ARs. This novel approach opens promising avenues for therapeutic interventions to effectively modulate inflammation and cell trafficking in diverse disease processes, promising impactful advancements in medical treatment.

CRISPR/Cas9 gene editing produced the THP-1_ADRA1BKO cell line, lacking α1B-AR. The T7 surveyor assay confirmed successful gene modification. Proximity Ligation Assay (PLA) demonstrated the absence of α1B-AR in THP-1_ADRA1BKO cells. Chemotaxis experiments revealed altered responses in THP-1_ADRA1BKO cells compared to wild-type THP-1 cells when exposed to CCL23, CCL2, CCL1, and CXCL12. The study highlights the importance of α1B/D-adrenergic receptors in mediating chemotactic responses and their potential as drug targets for modulating inflammation and cell trafficking.

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