The Immunomodulatory Effects and Mechanisms of Tim-3 Action in the Early Stage of Mice with Severe Acute Pancreatitis.
Iran J Immunol
; 17(1): 52-63, 2020 Mar.
Article
en En
| MEDLINE
| ID: mdl-32224541
ABSTRACT
BACKGROUND:
Tim-3 has been considered as an ideal target for the immunotherapy of inflammation, but it is unclear whether Tim-3 also plays an important role in acute pancreatitis (AP), as well.OBJECTIVE:
To identify the immunomodulatory effects and mechanisms of Tim-3 action in the early stages of severe acute pancreatitis in mice.METHODS:
Male BALB/c mice were randomly divided into sham injection group, severe acute pancreatitis group, and anti-Tim-3 treated group. Histopathological scores of the pancreas were calculated, pancreatic myeloperoxidase (MPO) activity was assessed. The concentrations of serum IL-6, IL-10, and TNF-α were evaluated by ELISA method. Quantitative RT-PCR was performed to detect the transcripts of Tim-3, IL-6, IL-10, TNF-α, and TLR4 in peritoneal macrophages. The levels of peritoneal macrophages Tim-3, TLR4, MyD88, and NF-kB p65 were measured by western blot analysis.RESULTS:
The pathological scores of the anti-Tim-3 treated group (11.5 ± 1.3) significantly increased compared with the sham (1.3 ± 0.5) and SAP groups (6.9 ± 1.0). Furthermore, the downregulation of Tim-3 significantly aggravated mouse pancreatic tissue damage. It was further shown that Tim-3 negatively regulated the production of pro-inflammatory cytokines, IL-6 and TNF-α, as well as anti-inflammatory cytokine IL-10. Of note, the negative regulation of inflammatory cytokines by Tim-3 was mediated by the activation of TLR4/MyD88 NF-kB signaling pathway.CONCLUSION:
Our study showed that Tim-3 might play an important role in the development of AP through regulating the inflammatory response.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pancreatitis
/
Receptor 2 Celular del Virus de la Hepatitis A
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Iran J Immunol
Año:
2020
Tipo del documento:
Article
País de afiliación:
China