Pro-inflammatory cytokine-driven PI3K/Akt/Sp1 signalling and H2S production facilitates the pathogenesis of severe acute pancreatitis.
Biosci Rep
; 37(2)2017 04 30.
Article
em En
| MEDLINE
| ID: mdl-28396512
ABSTRACT
Severe acute pancreatitis (SAP) is a disease usually associated with systemic organ dysfunction or pancreatic necrosis. Most patients with SAP suffer from defective intestinal motility in the early phase of the disease. Additionally, SAP-induced inflammation produces hydrogen sulphide (H2S) that impairs the gastrointestinal (GI) system. However, the exact mechanism of H2S in the regulation of SAP is yet to be elucidated. In the present paper, we used a rat model of SAP to evaluate the role of H2S on intestinal motility by counting the number of bowel movements and investigating the effect of H2S on inflammation. We treated colonic muscle cells (CMCs) with SAP plasma, tumour necrosis factor-α (TNF-α) or interleukin-6 (IL-6) and measured the expressions of H2S-producing enzymes cystathionine-γ-lyase (CSE), cystathionine-ß-synthase (CBS) and Sp1 and PI3K/Akt by using quantitative PCR, Western blotting and immunohistochemical detection. We used the PI3K inhibitor LY294002 and the siRNA si-Sp1 to suppress the activity of the PI3K/Akt/Sp1 signalling pathway. We found that, in the SAP rat model, H2S facilitated an inhibitory effect on intestinal motility and enhanced the inflammatory response caused by SAP (P<0.05). The expressions of CSE and CBS in CMCs were significantly increased after treatment with TNF-α or IL-6 (P<0.05). Blocking the PI3K/Akt/Sp1 pathway remarkably inhibited the synthesis of CSE and CBS. Our data demonstrated that H2S plays a vital role in the pathogenesis of SAP and that SAP is modulated by inflammation driven by the PI3K/Akt/Sp1 signalling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pancreatite
/
Proteínas Quinases
/
Transdução de Sinais
/
Citocinas
/
Fosfatidilinositol 3-Quinases
/
Proteínas Proto-Oncogênicas c-akt
/
Sulfeto de Hidrogênio
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biosci Rep
Ano de publicação:
2017
Tipo de documento:
Article