Becalming Type 17 Inflammation in Ulcerative Colitis

Simmons, Alison

doi:10.1016/j.immuni.2019.03.019

Cited by 3 publications

(3 citation statements)

References 10 publications

(9 reference statements)

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“…Pyroptosis is an innovative inflammatory programmed cell death accompanied by the release of IL-1β and IL-18 (Pellegrini et al, 2020;Liu F. et al, 2021), which are the main proinflammatory factors leading to UC (Nowarski et al, 2015;Chen and Simmons, 2019). Pyroptosis is associated with the activation of NLRP3, which binds to ASC to recruit caspase-1 to form an inflammatory complex.…”

Section: Discussionmentioning

confidence: 99%

The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation

Jia

Guo

et al. 2022

Front. Pharmacol.

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Huazhuojiedu decoction (HZJDD), a traditional Chinese medicine prescription, has been clinically proven to be an effective treatment for ulcerative colitis (UC). However, the mechanism of HZJDD in the treatment of UC remains unclear. This study combined network pharmacology with experimental validation to explore the potential mechanism of HZJDD on UC. First, the relationship network diagrams between HZJDD and UC were established based on multiple databases. Then, the HZJDD-UC intersection genes target network was constructed and Gene Ontology-Biological processes (GO-BP) analysis was performed to discover the potential pharmacological mechanism. Finally, the results of GO-BP were verified in dextran sulfate sodium salt (DSS) induced UC rats. The network pharmacology results showed that 119 active components and 146 potential targets were screened for HZJDD, and six of the top 15 biological processes belonged to inflammatory response, cellular response to hypoxia, and cellular response to lipopolysaccharide (LPS). The GO-BP results indicated that the mechanism of HZJDD treatment of UC was related to inflammation, oxidative stress, and the regulation of LPS. Animal experiments showed that HZJDD could significantly reduce the disease activity index (DAI) score, improve colon length, and effectively repair the histomorphological and micromorphological changes in DSS-induced UC rats. Moreover, HZJDD reduced the expressions of CRP, TNF-α, IL-6, LPS, IL-1β, and IL-18; downregulated the activity of MDA; and upregulated the activities of CAT, GSH, and SOD in DSS-induced UC rats. Furthermore, HZJDD suppressed the expression of the NLRP3/caspase-1 signaling pathway at the gene and protein levels to inhibit pyroptosis. Network pharmacology and animal experiments showed that HZJDD exerted a therapeutic effect on DSS-induced UC rats by reducing inflammation, oxidative stress, and restraining the NLRP3/caspase-1 signaling pathway to inhibit pyroptosis.

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Section: Discussionmentioning

confidence: 99%

The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation

Jia

Guo

et al. 2022

Front. Pharmacol.

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“…In fact, stimulation with IL-1β and IL-23 is sufficient to trigger abundant secretion of IL-17 by γδT cells in vitro, even in the absence of TCR stimulation 43 . IRF4 cooperates with STAT3 to regulate gene expression, and links IL-1R and IL-23R signaling pathways to IL-17 production 3 . STAT3 activation is crucial for RORγt expression in Th17 cells and also important for IL-17 production in γδT cells 57,58 .…”

Section: Discussionmentioning

confidence: 99%

“…The greatest increase in the incidence of UC is observed in newly industrialized countries, and the highest incidence and prevalence is recorded in Western countries, particularly in Europe and America 2 . Although the etiology of UC remains unclear, studies in recent years emphasize the importance of the dysregulation of immune responses, especially type-17 immune response, in the initiation, augmentation, and perpetuation of UC 3,4 . The type 17 immune response is mediated mainly by the activation of IL-17-producing cells, including αβT cells, γδT cells, and innate lymphoid cells (ILCs) [5][6][7] .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the activation of γδT17 cells through PPARγ–PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acid

Yun

Fang

et al. 2020

Cell Death Dis

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Type-17 immune response, mediated mainly by IL-17, plays a critical role in ulcerative colitis. Previously, we showed that madecassic acid (MA), the main active ingredient of Centella asiatica herbs for anti-colitis effect, ameliorated dextran sulfate sodium (DSS)-induced mouse colitis through reducing the level of IL-17. Here, we explore the effect of MA on the activation of γδT17 cells, an alternative source of IL-17 in colitis. In DSS-induced colitis mice, oral administration of MA decreased the number of γδT17 cells and attenuated the inflammation in the colon, and the anti-colitis effect of MA was significantly counteracted by redundant γδT17 cells, suggesting that the decrease in γδT17 cells is important for the anti-colitis effect of MA. In vitro, MA could inhibit the activation but not the proliferation of γδT17 cells at concentrations without evident cytotoxicity. Antibody microarray profiling showed that the inhibition of MA on the activation of γδT17 cells involved PPARγ–PTEN/Akt/GSK3β/NFAT signals. In γδT17 cells, MA could reduce the nuclear localization of NFATc1 through inhibiting Akt phosphorylation to promote GSK3β activation. Moreover, it was confirmed that MA inhibited the Akt/GSK3β/NFATc1 pathway and the activation of γδT17 cells through activating PPARγ to increase PTEN expression and phosphorylation. The correlation between activation of PPARγ, decrease in γδT17 cell number, and amelioration of colitis by MA was validated in mice with DSS-induced colitis. In summary, these findings reveal that MA inhibits the activation of γδT17 cells through PPARγ–PTEN/Akt/GSK3β/NFAT pathway, which contributes to the amelioration of colitis.

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Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro

Jie

Xiao

Qiao

et al. 2021

Journal of Ethnopharmacology

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Becalming Type 17 Inflammation in Ulcerative Colitis

Cited by 3 publications

References 10 publications

The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation

The potential mechanism of huazhuojiedu decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation

Inhibition of the activation of γδT17 cells through PPARγ–PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acid

Kuijieling decoction suppresses NLRP3-Mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro

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