Regulation of bradykinin receptor gene expression in human lung fibroblasts

Phagoo, Stephen B.; Yaqoob, Mohammed; Herrera-Martinez, Esteban; McIntyre, Peter; Jones, Caroline E.; Burgess, Gillian M.

doi:10.1016/s0014-2999(00)00323-x

Cited by 36 publications

(28 citation statements)

References 35 publications

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“…Currently it is generally accepted that the main receptor involved in angioedema attacks is the bradykinin receptor B2R with a minor, if any, role for B1R [7,16]. A main reason for this notion is that, in contrast to B2R, B1R is not expressed constitutively but rather is exposed by endothelial cells upon stimulation with cytokines [10][11][12]. However, B2R stimulation by BK is notorious for induction of hypotension [36] and it remains unclear why, in spite of detectable bradykinin levels in the circulation, hypotensive reactions are uncommon in symptomatic HAE patients [37,38].…”

Section: Discussionmentioning

confidence: 99%

C-reactive protein levels in hereditary angioedema

Hofman

Relan

Hack

2014

Clinical and Experimental Immunology

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SummaryHereditary angioedema (HAE) patients experience recurrent episodes of angioedema attacks that can be painful, disfiguring and even life-threatening. The disorder results from a mutation in the gene that controls the synthesis of C1-inhibitor (C1INH). C1INH is a major regulator of activation of the contact system. It is often assumed that attacks results from uncontrolled local activation of the contact system with subsequent formation of bradykinin. To evaluate the involvement of inflammatory reactions in HAE, we analysed C-reactive protein (CRP) levels. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. For the current study we analysed CRP levels when patients were asymptomatic, during a clinical attack and in a follow-up period, and correlated these with the clinical manifestations of the attack. Data from 68 HAE patients were analysed and included CRP levels on 273 occasions. While asymptomatic, 20% of the patients analysed had increased CRP. At the onset of the attack (P = 0·049) and during the next 24 h CRP rose significantly (P = 0·002) in patients with an abdominal location, and post-attack levels were significantly higher in these patients than in patients with attacks at other locations (P = 0·034). In conclusion, CRP levels are elevated in a substantial proportion of asymptomatic HAE patients. Levels of CRP increase significantly during an abdominal attack. These data suggest low-grade systemic inflammatory reactions in HAE patients as well as a triggering event for attacks that starts prior to symptom onset.

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Section: Discussionmentioning

confidence: 99%

C-reactive protein levels in hereditary angioedema

Hofman

Relan

Hack

2014

Clinical and Experimental Immunology

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“…Exposure to bacterial endotoxins or cytokines, tissue trauma, inflammation, anoxia (130), and myocardial infarction (154) are examples of inducing stimuli. IL-1β and tumor necrosis factor (TNF)-α induce the expression of the B1R in vitro (155,156) and in vivo (157,158).…”

Section: Receptors Expression and Regulatory Elements In Gene Promotersmentioning

confidence: 99%

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

et al. 2005

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Abstract. The kallikrein-kinin system is an endogenous metabolic cascade, triggering of which results in the release of vasoactive kinins (bradykinin-related peptides). This complex system includes the precursors of kinins known as kininogens and mainly tissue and plasma kallikreins. The pharmacologically active kinins, which are often considered as either proinflammatory or cardioprotective, are implicated in many physiological and pathological processes. The interest of the various components of this multi-protein system is explained in part by the multiplicity of its pharmacological activities, mediated not only by kinins and their receptors, but also by their precursors and their activators and the metallopeptidases and the antiproteases that limit their activities. The regulation of this system by serpins and the wide distribution of the different constituents add to the complexity of this system, as well as its multiple relationships with other important metabolic pathways such as the renin-angiotensin, coagulation, or complement pathways. The purpose of this review is to summarize the main properties of this kallikrein-kinin system and to address the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties.

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“…Human pulmonary fibroblasts have been demonstrated to express high levels of constitutive B 2 receptors and relatively low or undetectable levels of B 1 receptors under basal conditions (Schanstra et al, 1998;Haddad et al, 2000;Phagoo et al, 2000). To investigate the modulation of kinin B 1 and B 2 receptors, the experiments in this study were performed on human pulmonary fibroblasts incubated with pathogens or IL-1␤ in the absence of serum.…”

Section: Modulation Of B 1 Receptor Expression By Infectionmentioning

confidence: 99%

Infection-Induced Kinin B1 Receptors in Human Pulmonary Fibroblasts: Role of Intact Pathogens and p38 Mitogen-Activated Protein Kinase-Dependent Signaling

Phagoo

Reddi²,

Silvallana³

et al. 2005

The Journal of Pharmacology and Experimental Therapeutics

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Kinin B 1 receptors (B 1 R) are involved in many pathophysiological processes, and its expression is up-regulated in inflammatory pulmonary disease. Although bacteria can generate kinin peptides, the molecular signaling mechanisms regulating B 1 R during infection by intact pathogens is unknown. The serious opportunistic clinical isolate Burkholderia cenocepacia (B. cen.) belongs to the important B. cepacia complex (Bcc) of gramnegative pathogens that rapidly causes fatal pulmonary disease in hospitalized and immunocompromised patients and those with cystic fibrosis. We demonstrate here that B. cen. infection induced a rapid increase in B 1 R mRNA (1 h) proceeded by an increase in B 1 R protein expression (2 h), without affecting B 2 receptor expression in human pulmonary fibroblasts. The B 1 R response was dose-dependent and maximal by 6 to 8 h (3-to 4-fold increase), however, brief B. cen. infection could sustain B 1 R up-regulation. In contrast, nonclinical Bcc phytopathogens were much less B 1 R inducive. The protein synthesis inhibitor cycloheximide and transcriptional inhibitor actinomycin D abrogated the B 1 response to B. cen. indicating de novo B 1 R synthesis. B. cen. activated p38 mitogen-activated protein kinase (MAPK), and blocking p38 MAPK with the specific inhibitor 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB 203580) dramatically reduced B. cen.-induced B 1 R. Furthermore, B. cen. regulation of B 1 R was diminished by the anti-inflammatory glucocorticoid dexamethasone. In conclusion, this study is the first demonstration that infection with intact pulmonary pathogens like B. cen. positively modulates the selective expression of B 1 R. Thus, providing evidence that B 1 R regulation may be an important and novel mechanism in the inflammatory cascade in response to chronic pulmonary infection and disease.

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Regulation of bradykinin receptor gene expression in human lung fibroblasts

Cited by 36 publications

References 35 publications

C-reactive protein levels in hereditary angioedema

C-reactive protein levels in hereditary angioedema

The Kallikrein-Kinin System: Current and Future Pharmacological Targets

Infection-Induced Kinin B1 Receptors in Human Pulmonary Fibroblasts: Role of Intact Pathogens and p38 Mitogen-Activated Protein Kinase-Dependent Signaling

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