Increased blood concentration of des-Arg9-bradykinin in experimental allergic encephalomyelitis

Germain, L.; Barabé, J.; Galeano, C.

doi:10.1016/0022-510x(88)90069-x

Cited by 23 publications

(7 citation statements)

References 8 publications

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“…So far, only B 2 receptors have been implicated in causing centrally mediated hyperalgesia. However, in keeping with current observations of peripheral hyperalgesia, B 1 receptor involvement in chronic central inflammatory conditions should be further evaluated (see Germain et al 1988).…”

Section: Kinins and Central Painmentioning

confidence: 85%

Kinins and their receptors in hyperalgesia

Dray¹

1997

Can. J. Physiol. Pharmacol.

113

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Kinins (bradykinin, kallidin) are produced at sites of injury and inflammation and serve a critical role in signaling tissue distress as well as organising tissue responsiveness to injury. The acute activation and prolonged sensitization of fine afferents, to produce pain and hyperalgesia, are important in the protective responses that occur to minimize further tissue injury. These effects occur via activation of B2 receptors present on sensory neurons, resulting in a change of membrane excitability and altered cellular neurochemistry. B2 receptor activation of a variety of tissues including postganglionic sympathetic fibres stimulates the production of several proinflammatory mediators, including prostanoids and cytokines, which interact with kinins and contribute to inflammation and hyperalgesia. Increased expression of B1 receptors plays a prominent role in inflammatory hyperalgesia, but further characterization of the cellular mechanism is required. A role for kinins and kinin receptors in central pathophysiologies (trauma, ischemia, infection) needs examination. The evidence for modulation of nociception and central pain generation is compelling, as central bradykinin administration causes hyperalgesia, whereas B2 antagonists are antinociceptive. The basis for these effects should be urgently investigated. Such data will add further support to the utilization of bradykinin receptor antagonists for the treatment of peripheral and central pain.

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Section: Kinins and Central Painmentioning

confidence: 85%

Kinins and their receptors in hyperalgesia

Dray¹

1997

Can. J. Physiol. Pharmacol.

113

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“…Early studies in rabbits demonstrated significant differences in the levels of bradykinin and desArg 9 -bradykinin during EAE (Germain et al, 1988). Cleavage of bradykinin and kallidin by CPN generates desArg 9 -bradykinin and desArg 10 -kallidin, both of which mediate chronic inflammatory responses on binding to the B1 kinin receptor (Couture et al, 2001; Regoli and Barabe, 1980).…”

Section: Discussionmentioning

confidence: 99%

Carboxypeptidase N-deficient mice present with polymorphic disease phenotypes on induction of experimental autoimmune encephalomyelitis

Wetsel

Ramos

et al. 2014

Immunobiology

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Carboxypeptidase N (CPN) is a member of the carboxypeptidase family of enzymes that cleave carboxy-terminal lysine and arginine residues from a large number of biologically active peptides and proteins. These enzymes are best known for their roles in modulating the activity of kinins, complement anaphylatoxins and coagulation proteins. Although CPN makes important contributions to acute inflammatory events, little is known about its role in autoimmune disease. In this study we used CPN−/− mice in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Unexpectedly, we observed several EAE disease phenotypes in CPN−/− mice compared to wild type mice. The majority of CPN−/− mice died within five to seven days after disease induction, before displaying clinical signs of disease. The remaining mice presented with either mild EAE or did not develop EAE. In addition, CPN−/− mice injected with complete or incomplete Freund's adjuvant died within the same time frame and in similar numbers as those induced for EAE. Overall, the course of EAE in CPN−/− mice was significantly delayed and attenuated compared to wild type mice. Spinal cord histopathology in CPN−/− mice revealed meningeal, but not parenchymal leukocyte infiltration, and minimal demyelination. Our results indicate that CPN plays an important role in EAE development and progression and suggests that multiple CPN ligands contribute to the disease phenotypes we observed.

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“…For instance, high levels of the kallikrein-kinin components, namely des-Arg 9 -bradykinin (DABK), bradykinin, kallikrein-1 and kallikrein-6, as well as low-molecular-weight kininogens (KNGL), have been found in the CNS tissue and cerebrospinal fluid from both animals with EAE and MS patients [16], [17].…”

Section: Introductionmentioning

confidence: 99%

The Role of Kinin Receptors in Preventing Neuroinflammation and Its Clinical Severity during Experimental Autoimmune Encephalomyelitis in Mice

et al. 2011

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BackgroundMultiple sclerosis (MS) is a demyelinating and neuroinflammatory disease of the human central nervous system (CNS). The expression of kinins is increased in MS patients, but the underlying mechanisms by which the kinin receptor regulates MS development have not been elucidated.Methodology/Principal FindingsExperimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice by immunization with MOG35–55 peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Here, we report that blockade of the B1R in the induction phase of EAE markedly suppressed its progression by interfering with the onset of the immune response. Furthermore, B1R antagonist suppressed the production/expression of antigen-specific TH1 and TH17 cytokines and transcription factors, both in the periphery and in the CNS. In the chronic phase of EAE, the blockade of B1R consistently impaired the clinical progression of EAE. Conversely, administration of the B1R agonist in the acute phase of EAE suppressed disease progression and inhibited the increase in permeability of the blood-brain barrier (BBB) and any further CNS inflammation. Of note, blockade of the B2R only showed a moderate impact on all of the studied parameters of EAE progression.Conclusions/SignificanceOur results strongly suggest that kinin receptors, mainly the B1R subtype, play a dual role in EAE progression depending on the phase of treatment through the lymphocytes and glial cell-dependent pathways.

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Increased blood concentration of des-Arg9-bradykinin in experimental allergic encephalomyelitis

Cited by 23 publications

References 8 publications

Kinins and their receptors in hyperalgesia

Kinins and their receptors in hyperalgesia

Carboxypeptidase N-deficient mice present with polymorphic disease phenotypes on induction of experimental autoimmune encephalomyelitis

The Role of Kinin Receptors in Preventing Neuroinflammation and Its Clinical Severity during Experimental Autoimmune Encephalomyelitis in Mice

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