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. 2024 Sep;73(9):1459-1476.
doi: 10.1007/s00011-024-01909-1. Epub 2024 Jul 4.

Kinin B1 receptor and TLR4 interaction in inflammatory response

Carolina Batista  1   2 , João Victor Roza Cruz  1 , Joice Stipursky  1 , Fabio de Almeida Mendes  3 , João Bosco Pesquero  4
Affiliations

Kinin B1 receptor and TLR4 interaction in inflammatory response

Carolina Batista et al. Inflamm Res. 2024 Sep.

Abstract

Objective: We aimed to broaden our understanding of a potential interaction between B1R and TLR4, considering earlier studies suggesting that lipopolysaccharide (LPS) may trigger B1R stimulation.

Methods: We assessed the impact of DBK and LPS on the membrane potential of thoracic aortas from C57BL/6, B1R, or TLR4 knockout mice. Additionally, we examined the staining patterns of these receptors in the thoracic aortas of C57BL/6 and in endothelial cells (HBMEC).

Results: DBK does not affect the resting membrane potential of aortic rings in C57BL/6 mice, but it hyperpolarizes preparations in B1KO and TLR4KO mice. The hyperpolarization mechanism in B1KO mice involves B2R, and the TLR4KO response is independent of cytoplasmic calcium influx but relies on potassium channels. Conversely, LPS hyperpolarizes thoracic aorta rings in both C57BL/6 and B1KO mice, with the response unaffected by a B1R antagonist. Interestingly, the absence of B1R alters the LPS response to potassium channels. These activities are independent of nitric oxide synthase (NOS). While exposure to DBK and LPS does not alter B1R and TLR4 mRNA expression, treatment with these agonists increases B1R staining in endothelial cells of thoracic aortic rings and modifies the staining pattern of B1R and TLR4 in endothelial cells. Proximity ligation assay suggests a interaction between the receptors.

Conclusion: Our findings provide additional support for a putative connection between B1R and TLR4 signaling. Given the involvement of these receptors and their agonists in inflammation, it suggests that drugs and therapies targeting their effects could be promising therapeutic avenues worth exploring.

Keywords: Bradykinin B1 receptor; Des-Arg9-Bradykinin; Endothelial cells; Lipopolysaccharide; TLR4.

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