Role of NLR family pyrin domain-containing 3 inflammasome in the activation of pancreatic stellate cells

Journal Article · Thu Jul 15 04:00:00 EDT 2021 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2021.112634· OSTI ID:23195604

Li, Cai-Xia; Cui, Li-Hua; Zhang, Lan-Qiu; Yang, Lei; Zhuo, Yu-Zhen ^[1]; Cui, Nai-Qiang ^[1]; Zhang, Shu-Kun ^[1]

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1. Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Institute of Acute Abdominal Diseases of Integrated Traditional Chinese and Western Medicine, Tianjin Nankai Hospital, Nankai Clinical College, Tianjin Medical University, Tianjin, 300100 (China)

Highlights: • NLRP3 inflammasome was activated with the extension of activation time of PSCs. • LPS triggered PSCs activation through activating NLRP3 Inflammasome. • Inhibition of NLRP3 inflammasome mitigates the activation of PSCs. • NLRP3 inflammasome activates the TGF-β1/Smad3 signaling pathway in PSCs. NLRP3 inflammasome activation plays an important role in the development of pancreatic fibrosis. However, it is unclear whether the activation of the NLRP3 inflammasome is directly involved in the activation of Pancreatic stellate cells (PSCs). The aim of this study was to investigate the role and mechanism of the NLRP3 inflammasome in the activation of PSCs. In vivo, a rat model of chronic pancreatitis (CP) was induced by intravenous injection of dibutyltin dichloride (DBTC). In vitro, rat primary PSCs were isolated from pancreatic tissues and incubated with the NLRP3 inflammasome activator LPS, the NLRP3 inhibitor MCC950, or NLRP3 siRNA. The results showed that the expression of NLRP3, pro-Caspase-1, Caspase-1 and IL-18 was increased in the rat model of CP and during PSCs activation. LPS increased the protein levels of NLRP3, ASC, Caspase-1, IL-1β and IL-18 accompanied by the upregulation of α-SMA, Col I and FN expression. Moreover, MCC950 or NLPR3 siRNA decreased the expression of α-SMA, Col I, FN, TGF-β1 and p-Smad3. Furthermore, MCC950 reversed the LPS-induced upregulation of α-SMA, FN and Col Ⅰ expression in PSCs. This study revealed that the NLRP3 inflammasome is directly involved in the activation of PSCs in vivo and in vitro. Inhibiting NLRP3 suppresses the activation of PSCs through the TGF-β1/Smad3 pathway.

• OSTI ID: 23195604
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 404; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
DIGESTIVE SYSTEM DISEASES
FIBROSIS
IN VITRO
IN VIVO
INHIBITION
INTRAVENOUS INJECTION
LIPOPOLYSACCHARIDES
PANCREAS
PROTEINS
RATS