RGD Reference Report - The antagonist of the JAK-1/STAT-1 signaling pathway improves the severity of cerulein-stimulated pancreatic injury via inhibition of NF-κB activity. - Rat Genome Database

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The antagonist of the JAK-1/STAT-1 signaling pathway improves the severity of cerulein-stimulated pancreatic injury via inhibition of NF-κB activity.

Authors: Chen, Ping  Huang, Liya  Zhang, Yongping  Qiao, Minmin  Yao, Weiyan  Yuan, Yaozong 
Citation: Chen P, etal., Int J Mol Med. 2011 May;27(5):731-8. doi: 10.3892/ijmm.2011.632. Epub 2011 Mar 1.
RGD ID: 19165136
Pubmed: PMID:21369693   (View Abstract at PubMed)
DOI: DOI:10.3892/ijmm.2011.632   (Journal Full-text)

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is widely involved in cell migration, apoptosis and inflammation. However, its exact mechanisms in severe acute pancreatitis (SAP) remain unclear. The aim of this study was to explore the activity of the JAK/STAT signaling pathway in pancreatic injury, investigate the functional mechanisms of SAP in vitro, and thus elucidate the underlying therapeutic effects for SAP in vivo. The activation of the JAK-1/STAT-1 signaling pathway and the expessions of TNF-α, IL-1β and IL-6 proteins were investigated in AR42J cells induced with cerulein and treated with either PBS, RPM, or AG490. One group of cells was left untreated as a control group. Subsequently the activity of NF-κB was evaluated. Rats were given RPM or AG490 just before the induction of SAP, the severity of which was assessed at 24 h. The findings revealed that the up-regulated expressions of JAK-1/STAT-1, STAT-3 protein were closely correlated with the transcription of TNF-α, IL-1β, and IL-6 in cerulein-stimulated cells. Administration of RPM or AG490 decreased the activity of NF-κB and inhibited the release of TNF-α, IL-1β, and IL-6. The reflective markers of severity of SAP were also decreased by RPM or AG490 treatment compared to SAP rats. This study indicates that the JAK-1/STAT-1 signaling pathway activity is an early event in pancreatic inflammatory injury. Therefore, early treatment with its inhibitors might be beneficial for attenuation of pancreatic injury in SAP.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Acute Experimental Pancreatitis treatmentISOJak1 (Rattus norvegicus)19165136; 19165136 RGD 
Acute Experimental Pancreatitis treatmentIEP 19165136 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Jak1  (Janus kinase 1)

Genes (Mus musculus)
Jak1  (Janus kinase 1)

Genes (Homo sapiens)
JAK1  (Janus kinase 1)


Additional Information