Determination of bradykinin-(1–5) in inflammatory exudate by a new ELISA as a reliable indicator of bradykinin generation

Murakami, Masataka; Nishiyama, Kouichiro; Iguchi, Yoshiaki; Yao, Kazuo; Ogino, Michiko; Ohno, Takashi; Sunahara, Noriyuki; Katoh, Kazuyoshi; Tatemichi, Noriyuki; Takei, Yoshiyuki; Kikuchi, Makoto

doi:10.1007/bf02252938

Cited by 34 publications

(25 citation statements)

References 22 publications

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“…Collectively, these data demonstrated that exogenous bradykinin prevented deep vein thrombosis via reduced monocytes and HUVECs TF expression and adhesion of leukocytes to the endothelium. Furthermore, the angiotensin-converting enzyme breakdown product of bradykinin, Arg-Pro-Pro-Gly-Phe (RPPGF), is a stable metabolite of bradykinin [35,36], and this peptide has biological activity [37]. Further study indicated that RPPGF inhibited both α-and β-thrombin-induced platelet aggregation and secretion via binding to the active site of thrombin and the extracellular domain of PAR1 to prevent thrombin cleavage after Arg41 [18,38].…”

Section: Discussionmentioning

confidence: 99%

Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

Dong¹,

Chen²,

Feng³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Bradykinin has been shown to exert a variety of protective effects against vascular injury, and to reduce the levels of several factors involved in the coagulation cascade. A key determinant of thrombin generation is tissue factor (TF). However, whether bradykinin can regulate TF expression remains to be investigated. Methods: To study the effect of bradykinin on TF expression, we used Lipopolysaccharides (LPS) to induce TF expression in human umbilical vein endothelial cells and monocytes. Transcript levels were determined by RT-PCR, protein abundance by Western blotting. In the in vivo study, bradykinin and equal saline were intraperitoneally injected into mice for three days ahead of inferior cava vein ligation that we took to induce thrombus formation, after which bradykinin and saline were injected for another two days. Eventually, the mice were sacrificed and tissues were harvested for tests. Results: Exogenous bradykinin markedly inhibited TF expression in mRNA and protein level induced by LPS in a dose-dependent manner. Moreover, the NO synthase antagonist L-NAME and PI3K inhibitor LY294002 dramatically abolished the inhibitory effects of bradykinin on tissue factor expression. PI3K/Akt signaling pathway activation induced by bradykinin administration reduced the activity of GSK-3ß and MAPK, and reduced NF-κB level in the nucleus, thereby inhibiting TF expression. Consistent with this, intraperitoneal injection of C57/BL6 mice with bradykinin also inhibited the thrombus formation induced by ligation of inferior vena cava. Conclusion: Bradykinin suppressed TF protein expression in human umbilical vein endothelial cells and monocytes in vitro; in line with this, it inhibits thrombus formation induced by ligation of inferior vena cava in vivo.

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Section: Discussionmentioning

confidence: 99%

Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

Dong¹,

Chen²,

Feng³

et al. 2015

Cell Physiol Biochem

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“…bromelain had activity similar to 0.3 mg/kg i.p. dexamethasone (equivalent to 20 mg prednisone in a 70-kg human) in rat pleurisy models [11,12]. Bromelain had efficacy similar to or better than classic non-steroidal antiinflammatory agents (NSAIDs) in some rheumatologic studies in humans [14,16,19].…”

Section: Introductionmentioning

confidence: 99%

Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice

Hale

2004

International Immunopharmacology

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“…These include the experimental allergic encephalomyelitis (EAE) model of the human autoimmune disease multiple sclerosis (3), carrageenan-induced pleurisy in the rat (4)(5)(6), immunologically mediated arteriosclerosis in rat aortic allografts (7), rheumatologic diseases in mice and humans (8)(9)(10)(11)(12)(13), and allergic asthma (14) and rhinitis (15). Some studies demonstrated that bromelain had efficacy similar to standard anti-inflammatory drugs such as dexamethasone (5,6) or non-steroidal anti-inflammatory agents (NSAIDs) (8,10,11,16). Our previous studies showed that oral administration of 5 mg bromelain/day markedly decreased the development and severity of inflammatory bowel disease in IL-10 −/− mice (17).…”

Section: Introductionmentioning

confidence: 99%

Bromelain treatment decreases neutrophil migration to sites of inflammation

Fitzhugh

Shan

Dewhirst

et al. 2008

Clinical Immunology

116

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Bromelain, a mixture of proteases derived from pineapple stem, has been reported to have therapeutic benefits in a variety of inflammatory diseases, including murine inflammatory bowel disease. The purpose of this work was to understand potential mechanisms for this anti-inflammatory activity. Exposure to bromelain in vitro has been shown to remove a number of cell surface molecules that are vital to leukocyte trafficking, including CD128a/CXCR1 and CD128b/CXCR2 that serve as receptors for the neutrophil chemoattractant IL-8 and its murine homologues. We hypothesized that specific proteolytic removal of CD128 molecules by bromelain would inhibit neutrophil migration to IL-8 and thus decrease acute responses to inflammatory stimuli. Using an in vitro chemotaxis assay, we demonstrated a 40% reduction in migration of bromelain-vs. sham-treated human neutrophils in response to rhIL-8. Migration to the bacterial peptide analog fMLP was unaffected, indicating that bromelain does not induce a global defect in leukocyte migration. In vivo bromelain treatment generated a 50 -85% reduction in neutrophil migration in 3 different murine models of leukocyte migration into the inflamed peritoneal cavity. Intravital microscopy demonstrated that although in vivo bromelain treatment transiently decreased leukocyte rolling, its primary long-term effect was abrogation of firm adhesion of leukocytes to blood vessels at the site of inflammation. These changes in adhesion were correlated with rapid re-expression of the bromelain-sensitive CD62L/L-selectin molecules that mediate rolling following in vivo bromelain treatment and minimal re-expression of CD128 over the time period studied. Taken together, these studies demonstrate that bromelain can effectively decrease neutrophil migration to sites of acute inflammation and support the specific removal of the CD128 chemokine receptor as a potential mechanism of action.

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Determination of bradykinin-(1–5) in inflammatory exudate by a new ELISA as a reliable indicator of bradykinin generation

Cited by 34 publications

References 22 publications

Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

Exogenous Bradykinin Inhibits Tissue Factor Induction and Deep Vein Thrombosis via Activating the eNOS/Phosphoinositide 3-Kinase/Akt Signaling Pathway

Proteolytic activity and immunogenicity of oral bromelain within the gastrointestinal tract of mice

Bromelain treatment decreases neutrophil migration to sites of inflammation

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