Transcriptomic profiling of LPS-stimulated macrophages to evaluate the effects of GTS-21

The cholinergic anti-inflammatory pathway (CAP) is a neural mechanism that modulates immune responses. Macrophages express alpha 7 nicotinic acetylcholine receptors (alpha 7nAChRs), which play a crucial role in this pathway. To investigate downstream effects of alpha 7nAChR activation, we used GTS-21, a selective alpha 7nAChR agonist, in two macrophage cell lines. GTS-21 was applied both before and after LPS stimulation to assess its anti-inflammatory potential. In both experimental conditions, GTS-21 effectively reduced the expression of the pro-inflammatory cytokine TNF-alpha. Furthermore, transcriptomic analysis identified Ccl2 as a downstream gene that was significantly upregulated by LPS but suppressed following GTS-21 treatment, indicating that Ccl2 may be a key target in the anti-inflammatory action of CAP signaling via alpha 7nAChR.