Kinin B1 Receptor Up-Regulation after Lipopolysaccharide Administration: Role of Proinflammatory Cytokines and Neutrophil Influx

Abstract

Several studies have now clearly established the ability of LPS to induce bradykinin B1 receptor up-regulation in vivo and the functional relevance of this up-regulation for the pathophysiological effects of LPS. Using an in vivo system in which LPS is injected locally into the rat paw, we have examined the potential contribution of proinflammatory cytokines, NF-κB activation, and neutrophil influx for the functional and molecular up-regulation of the bradykinin B1 receptor. Treatment with LPS resulted in a rapid and sustained functional up-regulation of B1 receptors in the rat paw that correlated with the increase in B1 receptor mRNA levels. B1 receptor up-regulation is preceded by the rapid activation of the transcription factor NF-κB and the production of proinflammatory cytokines, including TNF-α and IL-1β. More importantly, blockade of NF-κB translocation, TNF-α, or IL-1β prevented the functional and molecular up-regulation of B1 receptors. Injection of LPS also induced the influx of neutrophils that followed the peak of cytokine production and associated with the persistent activation of NF-κB and functional B1 receptor up-regulation. Blockade of neutrophil influx with platelet-activating factor receptor antagonists or cell adhesion molecule blockers prevented B1 receptor up-regulation. Thus, by acting in cooperation and in a coordinated, timely manner, TNF-α, IL-1β, neutrophils, and the transcription factor NF-κB are major and essential players in the ability of LPS to induce B1 receptor expression in vivo.

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

“…Treatment with BCP prevented the increase in NAG activity, suggesting an impairment of mononuclear cell infiltration. BCP also decreases MPO activity in inflamed colons 53 and in rat paws treated with carrageenan 49 or LPS. 52 The reduction in cellular infiltration observed in the present study was associated with a decrease in colon damage.…”

“…48,49 BCP is a secondary metabolite found in many plant species, 50,51 and it exhibits long-lasting oral and topical anti-inflammatory properties in different inflammatory models. 49,52 Corroborating a previous report, the present study demonstrated that BCP, given orally, consistently ameliorated the inflammatory signs associated with DSS-induced colitis, such as decreased body weight and colon length and increased colonic tissue damage, 53 in both therapeutic and preventive treatment. In all parameters analyzed, preventive treatment with BCP was more effective than therapeutic treatment at the highest dose (50 mg/kg, p.o.…”

Bradykinin and des-Arg10-kallidin enhance the adhesion of polymorphonuclear leukocytes to extracellular matrix proteins and endothelial cells

“…The activation of these processes by cytokines is well recognized (Gumbiner, 1996;Meager, 1999;Mariscalsco, 2006). Regardless of a large body of evidence for a pro-migratory activity of kinins on leukocytes (Koyama et al, 2000;Passos et al, 2004;Arndt et al, 2006;Ehrenfeld et al, 2006;Bertram et al, 2007), no corroboration of kinin effects on adhesive 6processes have been observed. In this work, we demonstrated a regulation of PMN adhesive functions by the major kinin, BK, and des-Arg kinin metabolite, DAKD (Figure 1).…”

A Novel Nonpeptide Antagonist of the Kinin B1Receptor: Effects at the Rabbit Receptor

“…Experimental results support a role of inflammatory cytokines and nuclear factor-B in B 1 R induction (Ni et al, 1998;Schanstra et al, 1998;Sabourin et al, 2002b;Passos et al, 2004). In systems where the B 1 R expression is inducible over a ϳ2-to 6-h period by cytokine treatment or tissue injury, protein synthesis inhibitors prevent its surface expression and function (Marceau et al, 1998;Fortin et al, 2003b).…”