Please use this identifier to cite or link to this item: https://doi.org/10.4049/jimmunol.1102011
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dc.titleThe role of neutral endopeptidase in caerulein-induced acute pancreatitis
dc.contributor.authorKoh, Y.-H.
dc.contributor.authorMoochhala, S.
dc.contributor.authorBhatia, M.
dc.date.accessioned2016-07-08T07:19:38Z
dc.date.available2016-07-08T07:19:38Z
dc.date.issued2011-11-15
dc.identifier.citationKoh, Y.-H., Moochhala, S., Bhatia, M. (2011-11-15). The role of neutral endopeptidase in caerulein-induced acute pancreatitis. Journal of Immunology 187 (10) : 5429-5439. ScholarBank@NUS Repository. https://doi.org/10.4049/jimmunol.1102011
dc.identifier.issn00221767
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/125289
dc.description.abstractSubstance P (SP) is well known to promote inflammation in acute pancreatitis (AP) by interacting with neurokinin-1 receptor. However, mechanisms that terminate SP-mediated responses are unclear. Neutral endopeptidase (NEP) is a cell-surface enzyme that degrades SP in the extracellular fluid. In this study, we examined the expression and the role of NEP in caerulein-induced AP. Male BALB/c mice (20-25 g) subjected to 3-10 hourly injections of caerulein (50 μg/kg) exhibited reduced NEP activity and protein expression in the pancreas and lungs. Additionally, caerulein (10 -7 M) also downregulated NEP activity and mRNA expression in isolated pancreatic acinar cells. The role of NEP in AP was examined in two opposite ways: inhibition of NEP (phosphoramidon [5 mg/kg] or thiorphan [10 mg/kg]) followed by 6 hourly caerulein injections) or supplementation with exogenous NEP (10 hourly caerulein injections, treatment of recombinant mouse NEP [1 mg/kg] during second caerulein injection). Inhibition of NEP raised SP levels and exacerbated inflammatory conditions in mice. Meanwhile, the severity of AP, determined by histological examination, tissue water content, myeloperoxidase activity, and plasma amylase activity, was markedly better in mice that received exogenous NEP treatment. Our results suggest that NEP is anti-inflammatory in caerulein-induced AP. Acute inhibition of NEP contributes to increased SP levels in caerulein-induced AP, which leads to augmented inflammatory responses in the pancreas and associated lung injury. Copyright © 2011 by The American Association of Immunologists, Inc.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.4049/jimmunol.1102011
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentPHARMACOLOGY
dc.description.doi10.4049/jimmunol.1102011
dc.description.sourcetitleJournal of Immunology
dc.description.volume187
dc.description.issue10
dc.description.page5429-5439
dc.description.codenJOIMA
dc.identifier.isiut000296767300053
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