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Rho-kinase signalli...
Rho-kinase signalling regulates trypsinogen activation and tissue damage in severe acute pancreatitis.
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- Awla, Darbaz (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Hartman Magnusson, Hannes (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Abdulla, Aree (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Zhang, Songen (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Rahman, Milladur (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Regnér, Sara (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Thorlacius, Henrik (författare)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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(creator_code:org_t)
- 2011-01-12
- 2011
- Engelska.
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Ingår i: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 162, s. 648-658
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://europepmc.or...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background and purpose: Severe acute pancreatitis (SAP) is characterized by trypsinogen activation, infiltration of leucocytes and tissue necrosis but the intracellular signalling mechanisms regulating organ injury in the pancreas remain elusive. Rho-kinase is a potent regulator of specific cellular processes effecting several pro-inflammatory activities. Herein, we examined the role of Rho-kinase signalling in acute pancreatitis. Experimental approach: Pancreatitis was induced by infusion of taurocholate into the pancreatic duct in C57BL/6 mice. Animals were treated with a Rho-kinase inhibitor Y-27632 (0.5-5 mg kg(-1) ) before induction of pancreatitis. Key results: Taurocholate infusion caused a clear-cut increase in serum amylase, pancreatic neutrophil infiltration, acinar cell necrosis and oedema formation in the pancreas. Levels of pancreatic myeloperoxidase (MPO), macrophage inflammatory protein-2 (MIP-2), trypsinogen activation peptide (TAP) and lung MPO were significantly increased, indicating local and systemic disease. Inhibition of Rho-kinase activity dose-dependently protected against pancreatitis. For example, 5 mg kg(-1) Y-27632 reduced acinar cell necrosis, leucocyte infiltration and pancreatic oedema by 90%, 89% and 58% respectively as well as tissue levels of MPO by 75% and MIP-2 by 84%. Moreover, Rho-kinase inhibition decreased lung MPO by 75% and serum amylase by 83%. Pancreatitis-induced TAP levels were reduced by 61% in Y-27632-treated mice. Inhibition of Rho-kinase abolished secretagogue-induced activation of trypsinogen in pancreatic acinar cells in vitro. Conclusions and Implications: Our novel data suggest that Rho-kinase signalling plays an important role in acute pancreatitis by regulating trypsinogen activation and subsequent CXC chemokine formation, neutrophil infiltration and tissue injury. Thus, these results indicate that Rho-kinase may constitute a novel target in the management of SAP.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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