CCR1 Antagonism by BX471 Attenuates Neuroinflammation and Apoptosis: Preliminary Findings From an In Vitro Model of Neuronal Injury

Neuronal injury as traumatic brain injury (TBI) triggers a complex pathophysiological cascade involving inflammatory and apoptosis processes. BX471 is a selective C-C chemokine receptor type 1 (CCR1) antagonist that showed a promising effect in modulating neuroinflammation in central nervous system (CNS) disorders. In this study, we investigated the neuroprotective effect of BX471 on the inflammatory pathway and apoptotic process in an in vitro model of induced-neuronal injury using SH-SY5Y neuroblastoma cells. Firstly, cytotoxicity was assessed by MTT assay to determine the optimal effective concentrations and the best temporal window for BX471 activity. Then, SH-SY5Y cells were subjected to a scratch injury to mimic a neuronal injury and were treated with different concentrations of BX471. ELISA and qRT-PCR were used to analyze the expression level of the CCR1/chemokines axis (CCR1, RANTES, MIP-1α), inflammatory markers (TNF-α, IL-1β, IL-6, NF-κB, IκBα, and PPAR𝛾), and the apoptotic pathway (Bcl2, BAX, P53, and cleaved caspase 3). The results showed that BX471 significantly improved the cell viability and inhibited the CCR1/chemokine axis and pro-inflammatory cytokines as well as modulating the apoptotic course. Overall, these results suggest that BX471 may reduce neuronal injury by inhibiting neuroinflammation and apoptosis, and that its neuroprotective effect, mediated through the CCR1 signaling pathway, deserves further investigation in in vivo models.