Tu1818 - Vitamin a Modulates Mucosal Inflammation by Augmenting Th1/Th17 Differentiation in Inflammatory Bowel Disease

Rampal, Ritika; Wari, Mohamad Nahidul; Singh, Amit; Das, Ujjwal; Bopanna, Sawan; Jain, Saransh; Gupta, Viney; Velpandian, Thirumurthy; Kedia, Saurabh; Kumar, Dhiraj; Awasthi, Amit; Ahuja, Vineet

doi:10.1016/s0016-5085(18)33444-9

Cited by 3 publications

(3 citation statements)

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“…This speculation is supported by pharmacology that TSPO binding drugs, PK11195 and Ro5-4864 could accelerate recovery after DSSinduced UC (Ostuni et al, 2010). Although the extent of TSPOmediated action remains unclear, positive and negative outcomes in DSS-induced UC have been reported for relatively low-affinity TSPO binding molecules such as curcumin (Li et al, 2013;Liu et al, 2013;Guo et al, 2022) and retinoic acid (Oehlers et al, 2012;Li et al, 2013;Rampal et al, 2021).…”

Section: Discussionmentioning

confidence: 98%

Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

et al. 2022

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In human patients and animal models of ulcerative colitis (UC), upregulation of the mitochondrial translocator protein (TSPO) in the colon is consistent with inflammation. Although the molecular function for TSPO remains unclear, it has been investigated as a therapeutic target for ameliorating UC pathology. In this study, we examined the susceptibility of Tspo gene-deleted (Tspo−/−) mice to insults as provided by the dextran sodium sulfate (DSS)-induced acute UC model. Our results show that UC clinical signs and pathology were severely exacerbated in Tspo−/− mice compared to control Tspofl/fl cohorts. Histopathology showed extensive inflammation and epithelial loss in Tspo−/− mice that caused an aggravated disease. Colonic gene expression in UC uncovered an etiology linked to precipitous loss of epithelial integrity and disproportionate mast cell activation assessed by tryptase levels in Tspo−/− colons. Evaluation of baseline homeostatic shifts in Tspo−/− colons revealed gene expression changes noted in elevated epithelial Cdx2, mast cell Cd36 and Mcp6, with general indicators of lower proliferation capacity and elevated mitochondrial fatty acid oxidation. These findings demonstrate that intact physiological TSPO function serves to limit inflammation in acute UC, and provide a systemic basis for investigating TSPO-targeting mechanistic therapeutics.

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Section: Discussionmentioning

confidence: 98%

Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

et al. 2022

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“…Retinoic acid (RA), one of the active products of Vitamin A, exhibits an anti-inflammatory phenotype by promoting CD4 + T-cell differentiation and production of TGF-β and IL-10 and by inhibiting the differentiation of both Th1 and Th17 cells, and alleviates DSS-induced IBD (Coombes and Powrie, 2008). However, in the mucosa of UC patients, RA levels were positively correlated with IL-17 and IFNγ expression on CD4 and CD8 T cells and negatively correlated with IL-10-expressing CD4 + T cells, suggesting dual effect of RA in colon inflammation (Rampal et al, 2021). A study reported that 19.6% of CD and 21.6% of UC were found to exhibit iron deficiency anemia associated with malabsorption in patients with IBD (Madanchi et al, 2018).…”

Section: Dietary Therapeuticsmentioning

confidence: 97%

The role of complex interactions between the intestinal flora and host in regulating intestinal homeostasis and inflammatory bowel disease

Cheng

et al. 2023

Front. Microbiol.

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Pharmacological treatment of inflammatory bowel disease (IBD) is inefficient and difficult to discontinue appropriately, and enterobacterial interactions are expected to provide a new target for the treatment of IBD. We collected recent studies on the enterobacterial interactions among the host, enterobacteria, and their metabolite products and discuss potential therapeutic options. Intestinal flora interactions in IBD are affected in the reduced bacterial diversity, impact the immune system and are influenced by multiple factors such as host genetics and diet. Enterobacterial metabolites such as SCFAs, bile acids, and tryptophan also play important roles in enterobacterial interactions, especially in the progression of IBD. Therapeutically, a wide range of sources of probiotics and prebiotics exhibit potential therapeutic benefit in IBD through enterobacterial interactions, and some have gained wide recognition as adjuvant drugs. Different dietary patterns and foods, especially functional foods, are novel therapeutic modalities that distinguish pro-and prebiotics from traditional medications. Combined studies with food science may significantly improve the therapeutic experience of patients with IBD. In this review, we provide a brief overview of the role of enterobacteria and their metabolites in enterobacterial interactions, discuss the advantages and disadvantages of the potential therapeutic options derived from such metabolites, and postulate directions for further research.

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“…However, etanercept (an antagonist of TNF-α) markedly reduced the levels of colonic inflammation (Popivanova et al, 2008). The Th17-derived Th1 cells responsible for several autoimmune diseases, including UC, are thought to provide the major pathogenic effector population for the diseases (Rampal et al, 2021;Bhaumik and Basu, 2017). The IL-6 can cause activation of signal transducer and activator of transcription (STAT)3, which induces IL-17 (including IL-17A and IL-17F) via activation of retinoic acid-related orphan receptor gamma t (RORγt) (Bhaumik and Basu, 2017).…”

Section: Pro-inflammatory Regulation: Pro-inflammatory T Cells and Re...mentioning

confidence: 99%

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis

et al. 2022

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Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein–protein interaction networks and herb–ingredient–target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)–Akt signaling pathway, advanced glycosylation end product (AGE)–RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.

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Tu1818 - Vitamin a Modulates Mucosal Inflammation by Augmenting Th1/Th17 Differentiation in Inflammatory Bowel Disease

Cited by 3 publications

References 0 publications

Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

The role of complex interactions between the intestinal flora and host in regulating intestinal homeostasis and inflammatory bowel disease

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis

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