Role of Kinin B2 Receptor Signaling in Astrocyte-driven Neuroinflammation

Abstract The kallikrein–kinin system (KKS) plays a key role in inflammatory responses, but its specific contribution to neuroinflammation remains to be fully elucidated. The bradykinin B 2 receptor (B 2 R), a principal effector of the KKS, is widely expressed in both neuronal and glial cells in the rodent and human brain. In this study, we investigated the molecular contribution of B 2 R to neuroinflammation using complementary in vitro and in vivo models. Lipopolysaccharide (LPS) stimulation significantly upregulated B 2 R mRNA expression in primary astrocyte cultures and in the cortical tissue of wild-type mice. Pharmacological blockade of B 2 R in astrocytes markedly suppressed the LPS-induced proinflammatory gene expression. In contrast, B 2 R antagonism in vivo resulted in only partial attenuation of the neuroinflammatory response. Together, these findings suggest cell type–specific roles for B 2 R and underscore its key contribution to astrocyte-mediated neuroinflammation. Graphical Abstract B 2 R antagonism highlights cell type–specific roles in neuroinflammation. B 2 R pharmacological antagonism suppresses proinflammatory gene expression in astrocytes but shows limited in vivo efficacy, indicating differential functions across brain cell types.