The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics

Jang, Dan-In; Lee, A-Hyeon; Shin, Hea Kyeong; Song, Hyo-Ryeong; Park, Jong-Hwi; Kang, Tae-Bong; Lee, Sang-Ryong; Yang, Seung‐Hoon

doi:10.3390/ijms22052719

Cited by 715 publications

(535 citation statements)

References 94 publications

Supporting

Mentioning

377

Contrasting

Unclassified

Order By: Relevance

“…This was consistent with our analysis of immune infiltration differentiation between normal and NAFLD liver tissues. According to our GSVA analysis, several pathways are associated with OPTN, including the NF-kB-mediated TNF-α pathway and the interferon α pathway, both of which regulate immunity and inflammation ( Vidal, 2020 ; Jang et al, 2021 ). TNF-α has become a major inducer of nutrient and obesity related NAFLD ( Perseghin et al, 2003 ; Shoelson et al, 2006 ), and the level of serum TNF-α in patients with NAFLD increased significantly ( Assuncao et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of NAFLD and the Therapeutic Target Identified

Wen

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Objective: Non-alcoholic fatty liver disease (NAFLD) is a serious health threat worldwide. The aim of this study was to comprehensively describe the metabolic and immunologic characteristics of NAFLD, and to explore potential therapeutic drug targets for NAFLD.Methods: Six NAFLD datasets were downloaded from the Gene Expression Omnibus (GEO) database, including GSE48452, GSE63067, GSE66676, GSE89632, GSE24807, and GSE37031. The datasets we then used to identify and analyze genes that were differentially expressed in samples from patients with NAFLD and normal subjects, followed by analysis of the metabolic and immunologic characteristics of patients with NAFLD. We also identified potential therapeutic drugs for NAFLD using the Connectivity Map (CMAP) database. Moreover, we constructed a prediction model using minimum depth random forest analysis and screened for potential therapeutic targets. Finally, therapeutic targets were verified in a fatty liver model stimulated by palmitic acid (PA).Results: A total of 1,358 differentially expressed genes (DEGs) were obtained, which were mainly enriched in carbohydrate metabolism, lipid metabolism, and other metabolic pathways. Immune infiltration analysis showed that memory B cells, regulatory T cells and M1 macrophage were significantly up-regulated, while T cells follicular helper were down regulated in NAFLD. These may provide a reference for the immune-metabolism interaction in the pathogenesis of NAFLD. Digoxin and helveticoside were identified as potential therapeutic drugs for NAFLD via the CMAP database. In addition, a five-gene prediction model based on minimum depth random forest analysis was constructed, and the receiver operating characteristic (ROC) curves of both training and validation set reached 1. The five candidate therapeutic targets were ENO3, CXCL10, INHBE, LRRC31, and OPTN. Moreover, the efficiency of hepatocyte adipogenesis decreased after OPTN knockout, confirming the potential use of OPTN as a new therapeutic target for NAFLD.Conclusion: This study provides a deeper insight into the molecular pathogenesis of NAFLD. We used five key genes to construct a diagnostic model with a strong predictive effect. Therefore, these five key genes may play an important role in the diagnosis and treatment of NAFLD, particularly those with increased OPTN expression.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of NAFLD and the Therapeutic Target Identified

Wen

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…TNF‐α is a pleiotropic pro‐inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signaling events within cells, leading to necrosis or apoptosis (Chu, 2013; Jang et al., 2021). TNF‐α can also cause tumor cell necrosis and apoptosis, and it is a potent activator of NF‐κB (Yu et al., 2020).…”

Section: Discussionmentioning

confidence: 99%

Lagerstroemia speciosa (L.) Pers., ethanolic extract attenuates simultaneously administered isoniazid‐ and dapsone‐induced hepatotoxicity in rats

Singh

Ezhilarasan

2021

J Food Biochem

View full text Add to dashboard Cite

Herbal tea of Lagerstroemia speciosa Pers., commonly known as banaba, has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti‐inflammatory efficacies. Drug‐induced liver injury is a common cause of acute liver failure. Isoniazid (INH) is used as the first‐line treatment for tuberculosis; clinical and experimental studies have reported an abnormal liver function after INH therapy. Dapsone (DDS) is used for leprosy and other infections. This study investigates the hepatoprotective effect of ethanolic banaba leaves extract (EBLE) against simultaneously administered INH‐ and DDS‐induced hepatotoxicity in rats. DDS (30 mg/kg, i.p.) and INH (50 mg/kg. p.o.) were administered simultaneously for 30 days. In separate groups, rats were posttreated orally with EBLE (500 mg/kg) and silymarin (100 mg/kg) for 30 days after INH + DDS administration. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers, and histopathology were done. Simultaneous administration of INH‐ and DDS‐induced significant elevation of marker enzymes of hepatotoxicity in the serum. This treatment also increased lipid peroxidation and pro‐inflammatory markers (tumor necrosis factor alpha, transforming growth factor beta, and nuclear factor kappa B) expressions and decreased intracellular antioxidants such as superoxide dismutase, catalase, and glutathione in the liver tissue. All these abnormalities were significantly mitigated after EBLE and SIL posttreatments. The results of this study suggest that EBLE and silymarin can be protective against INH + DDS‐induced hepatotoxicity. Practical applications Herbal tea contain Lagerstroemia speciosa leaves are used in several Southeast Asian countries due to its rich antioxidant and inflammatory properties. This study showed the hepatoprotective efficacy of L. speciosa ethanolic extract against simultaneously administered dapsone‐ and isoniazid‐induced hepatotoxicity in rats. L. speciosa administration was found to decrease dapsone‐ and isoniazid‐induced oxidative stress and hepatic inflammation. L. speciosa herbal tea can reduce drug‐induced hepatic complications as it contains phytochemicals such as corosolic acid, gallic acid, ellagic acid and berberine and are implicated for its hepatoprotective effect. Therefore, L. speciosa extract can be used for drug‐induced liver injury.

show abstract

“…These cells can specifically secrete various cytokines to regulate the immune system. For example, Th1 cells can secrete tumor necrosis factor α (TNF-α) to initiate a variety of proinflammatory responses [53]. Th17 cells are involved in the activation and recruitment of neutrophils [54].…”

Section: Mechanisms Of Bifidobacterium Longum Inmentioning

confidence: 99%

Bifidobacterium Longum: Protection against Inflammatory Bowel Disease

Yao

Zhao

Wang

et al. 2021

Journal of Immunology Research

106

View full text Add to dashboard Cite

The prevalence of inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), increases gradually worldwide in the past decades. IBD is generally associated with the change of the immune system and gut microbiota, and the conventional treatments usually result in some side effects. Bifidobacterium longum, as colonizing bacteria in the intestine, has been demonstrated to be capable of relieving colitis in mice and can be employed as an alternative or auxiliary way for treating IBD. Here, the mechanisms of the Bifidobacterium longum in the treatment of IBD were summarized based on previous cell and animal studies and clinical trials testing bacterial therapies. This review will be served as a basis for future research on IBD treatment.

show abstract

The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics

Cited by 715 publications

References 94 publications

Comprehensive Analysis of NAFLD and the Therapeutic Target Identified

Comprehensive Analysis of NAFLD and the Therapeutic Target Identified

Lagerstroemia speciosa (L.) Pers., ethanolic extract attenuates simultaneously administered isoniazid‐ and dapsone‐induced hepatotoxicity in rats

Bifidobacterium Longum: Protection against Inflammatory Bowel Disease

Contact Info

Product

Resources

About