Cell-permeable Tat-NBD peptide attenuates rat pancreatitis and acinus cell inflammation response
| Autor: | Wen-Rui Xie, Xue-Jin Liu, Ken Chen, You-Ming Long, Hui Wang |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Taurocholic Acid
Lipopolysaccharide Interleukin-1beta Inflammation Peptide Cell Line Rats Sprague-Dawley chemistry.chemical_compound Acinus medicine Animals Amino Acid Sequence RNA Messenger Peptide sequence chemistry.chemical_classification Chemistry Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Gastroenterology NF-kappa B General Medicine Original Articles medicine.disease Molecular biology Peptide Fragments Rats medicine.anatomical_structure Amino Acid Substitution Pancreatitis Cell culture Gene Products tat Tumor necrosis factor alpha lipids (amino acids peptides and proteins) medicine.symptom Peptides |
| Zdroj: | World journal of gastroenterology. 15(5) |
| ISSN: | 2219-2840 |
| Popis: | AIM: To investigate the effects of Tat-NEMO-binding domain (NBD) peptide on taurocholate-induced pancreatitis and lipopolysaccharide (LPS)-stimulated AR42J acinus cells inflammatory response in rats. METHODS: Sodium taurocholate (5%) was used to induce the pancreatitis model. Forty-eight rats from the taurocholate group received an intravenous bolus of 13 mg/kg Tat-NBD (wild-type, WT) peptide, Tat-NBD (mutant-type, MT) peptide, NBD peptide or Tat peptide. The pancreatic histopathology was analyzed by hematoxylin staining. LPS was added to the culture medium to stimulate the AR42J cells. For pretreatment, cells were incubated with different peptides for 2 h before LPS stimulation. Expression of IL-1β and TNF-α mRNA was analyzed using a semi-quantitative reverse-transcript polymerase chain reaction (RT-PCR) method. IL-1β and TNF-α protein in culture medium were detected by enzyme linked immunosorbent assay (ELISA). NF-κB DNA-binding in pancreas was examined by electrophoretic mobility shift assays. P65 expression of AR42J was determined by Strept Actividin-Biotin Complex (SABC) method. RESULTS: Pretreatment with Tat-NBD (WT) peptide at a concentration of 13 mg/kg body wt showed beneficial effect in pancreaitis model. LPS (10 mg/L) resulted in an increase of IL-1β mRNA, IL-1β protein, TNF-α mRNA and TNF-α protein, whereas significantly inhibitory effects were observed when cells were incubated with Tat-NBD (WT). Consisting with p65 expression decrease analyzed by SABC method, NF-κB DNA-binding activity significantly decreased in Tat-NBD (WT) pretreatment group, especially at the largest dose. No significant changes were found in the control peptide group. CONCLUSION: Our result supports that active NF-κB participates in the pathogenesis of STC-induced acute pancreatitis in rats. Tat-NBD (WT) peptide has anti-inflammatory effects in this model and inhibits the inflammation of acinus simulated by LPS. |
| Databáze: | OpenAIRE |
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