A modular map of Bradykinin-mediated inflammatory signaling network

Abstract

Bradykinin, a member of the kallikrein‐kinin system (KKS), is associated with an inflammatory response pathway with diverse vascular permeability functions, including thrombosis and blood coagulation. In majority, bradykinin signals through Bradykinin Receptor B2 (B2R). B2R is a G protein‐coupled receptor (GPCR) coupled to G protein family such as Gαqs, Gαq/Gα11, Gαi1, and Gβ1γ2. B2R stimulation leads to the activation of a signaling cascade of downstream molecules such as phospholipases, protein kinase C, Ras/Raf‐1/MAPK, and PI3K/AKT and secondary messengers such as inositol‐1,4,5‐trisphosphate, diacylglycerol and Ca2+ ions. These secondary messengers modulate the production of nitric oxide or prostaglandins. Bradykinin‐mediated signaling is implicated in inflammation, chronic pain, vasculopathy, neuropathy, obesity, diabetes, and cancer. Despite the biomedical importance of bradykinin, a resource of bradykinin‐mediated signaling pathway is currently not available. Here, we developed a pathway resource of signaling events mediated by bradykinin. By employing data mining strategies in the published literature, we describe an integrated pathway reaction map of bradykinin consisting of 233 reactions. Bradykinin signaling pathway events included 25 enzyme catalysis reactions, 12 translocations, 83 activation/inhibition reactions, 11 molecular associations, 45 protein expression and 57 gene regulation events. The pathway map is made publicly available on the WikiPathways Database with the ID URL: https://www.wikipathways.org/index.php/Pathway:WP5132. The bradykinin‐mediated signaling pathway map will facilitate the identification of novel candidates as therapeutic targets for diseases associated with dysregulated bradykinin signaling.

Retrospective Analysis of the Effect of Lidocaine Combined with Methylprednisolone on Pain Control After Uterine Artery Embolization

“…BKs serve as pain mediators that chemoattract neutrophils and inflammatory factors and participate in the process of inflammatory pain ( 24 ). Additionally, BKs can induce the release of inflammatory cytokines such as IL-6 and IL-8 through the NF-kB signaling pathway ( 25 ). Methylprednisolone produces significant anti-inflammatory effects by inhibiting the NF-kB pathway and upregulating anti-inflammatory mediators ( 13 ).…”

Activation of bradykinin receptor B1 promotes desensitization of CXCR2 in neutrophils during severe sepsis and contributes to disease progression in mice

“…The lung protein extracts were electrophoresed on a 12% polyacrylamide-SDS gel and transferred to nitrocellulose membranes according to established methods (8). The membranes were treated with specific primary antibodies (Santa Cruz Biotechnology, Santa Cruz, CA, USA), and then treated with the corresponding HRP-conjugated secondary antibody.…”

Chronic Pain after Bone Fracture: Current Insights into Molecular Mechanisms and Therapeutic Strategies

“…The appearance of local tissue damage and inflammation after fracture leads to activation of the kallikrein system. Kallikrein is essentially a proteolytic enzyme that produces bradykinin (BK), a related peptide (Lys-BK), and its active metabolites from kininogen substrates [ 72 ]. Kinin is involved in the regulation of inflammatory processes by activating two G protein-coupled receptors, B1 and B2 [ 71 ].…”