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GSK-3β activates NF-κB to aggravate caerulein-induced early acute pancreatitis in mice.

ABSTRACT:

Background

Acute pancreatitis is a life-threatening disease which causes considerable morbidity and mortality. However, no specific and effective treatments are currently available for this critical condition, which is mainly due to the insufficient understanding of the early cellular events in the initial phase of acute pancreatitis. Previous researchers have reported that two independent events, intra-acinar trypsinogen and NF-κB activation, are of equal importance in the early development of acute pancreatitis. GSK-3β, an essential molecule in multiple physiopathological processes including inflammation, is associated with the expression of the NF-κB pathway.

Methods

We investigated whether GSK-3β affected the expression of cytokines produced by intra-acinar cells and aimed to determine the probable regulatory mechanism by using single allele GSK-3β-deficient mice.

Results

Our data showed that IL-6 and TNF-α mRNA expression in pancreatic tissue and serum IL-6 and TNF-α were significantly decreased. Meanwhile, pancreatic phospho-NF-κB p65 (ser536) protein expression in GSK-3β ^+/- mice was lower than that in wild type (WT) mice.

Conclusions

GSK-3β may activate intra-acinar NF-κB signaling to promote the production of proinflammatory cytokines, which then induces the recruitment of inflammatory cells and activation of the cytokine cascade, further promoting local and systemic inflammation and ultimately aggravating acute pancreatitis. These findings strongly indicate that GSK-3β may be a potential treatment target for acute pancreatitis.

SUBMITTER: Fu X

PROVIDER: S-EPMC8667130 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

<i>GSK-3β</i> activates <i>NF-κB</i> to aggravate caerulein-induced early acute pancreatitis in mice.

Fu Xiaoying X Zhong Xi X Chen Xudong X Yang Dujiang D Zhou Zongguang Z Liu Yong Y

Annals of translational medicine 20211101 22

<h4>Background</h4>Acute pancreatitis is a life-threatening disease which causes considerable morbidity and mortality. However, no specific and effective treatments are currently available for this critical condition, which is mainly due to the insufficient understanding of the early cellular events in the initial phase of acute pancreatitis. Previous researchers have reported that two independent events, intra-acinar trypsinogen and <i>NF-κB</i> activation, are of equal importance in the early ...[more]

PMID: 34988204

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