Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction

Hermanns, Heike M.; Wohlfahrt, Julia; Mais, Christine; Hergovits, Sabine; Jahn, Daniel; Geier, Andreas

doi:10.1515/hsz-2015-0277

Cited by 11 publications

(4 citation statements)

References 97 publications

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“…PLEK might be a susceptibility locus for venous thromboembolism, and its expression is increased in UC, periodontitis, and celiac disease (Song et al, 2015;Pascual et al, 2016;Lindstrom et al, 2019;Medrano et al, 2019). In diabetes, PLEK has been reported to promote the secretion of proinflammatory cytokines such as TNF-α and IL-1β in mononuclear phagocytes; these cytokines have already been linked to increased risk of UC and RA (Ding et al, 2007;Hermanns et al, 2016). We speculate that SRGN and PLEK are involved in the pathogenesis of UC and RA through the increase in inflammatory factors.…”

Section: Discussionmentioning

confidence: 87%

Identification of Common Differentially Expressed Genes and Potential Therapeutic Targets in Ulcerative Colitis and Rheumatoid Arthritis

Chen

Lai

et al. 2020

Front. Genet.

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Ulcerative colitis (UC) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases (IMIDs) with similar symptoms and common genomics. However, the relationship between UC and RA has not been investigated thoroughly. Therefore, this study aimed to establish the differentially expressed genes (DEGs) and potential therapeutic targets in UC and RA. Three microarray datasets (GSE38713, GSE1919, and GSE12251) were selected from the Gene Expression Omnibus (GEO) database for analysis. We used R software to identify the DEGs and performed enrichment analyses. Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software were used to construct the protein-protein interaction (PPI) network and identify the hub genes. A regulatory network based on the constructed PPI was generated using StarBase and PROMO databases. We identified a total of 1542 and 261 DEGs in UC and RA. There were 169 common DEGs identified in both UC and RA, including 63 upregulated genes (DEGs1) and nine downregulated genes (DEGs2). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs1 and DEGs2 in the PPI network revealed that the genes enriched were involved in immunity. A total of 45 hub genes were selected based on high scores of correlation; three hub genes (SRGN, PLEK, and FCGR3B) were found to be upregulated in UC and RA, and downregulated in UC patients with response to infliximab treatment. The identification of novel DEGs and hub genes in the current study contributes to a novel perception for latent functional mechanisms and presents potential prognostic indicators and therapeutic targets in UC and RA.

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Section: Discussionmentioning

confidence: 87%

Identification of Common Differentially Expressed Genes and Potential Therapeutic Targets in Ulcerative Colitis and Rheumatoid Arthritis

Chen

Lai

et al. 2020

Front. Genet.

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“…Intestinal immunity plays a significant role in the pathogenesis of ulcerative colitis (Dong et al, 2020), and proinflammatory cytokines TNF-α, IL-1β, IL-6, and INF-γ are important mediators of immune response (Dinarello, 2011;Hermanns et al, 2016;Lazaridis et al, 2017;Nikolaus et al, 2018). In LPS-induced ulcerative colitis, a large number of inflammatory infiltrating cells secrete high levels of proinflammatory cytokines.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of recombinant lactoferrin with different iron saturations on enteritis injury in young mice

Fan¹,

Yao²,

et al. 2022

Journal of Dairy Science

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Infant intestinal development is immature and, thus, is vulnerable to bacterial and viral infections, which damage intestinal development and even induce acute enteritis. Numerous studies have investigated that lactoferrin (LF) has protective effects on the intestine and may play a role in preventing intestinal inflammation in infants. Lactoferrin is divided into 2 types, namely apo-LF and holo-LF, depending on the degree of iron saturation, which may affect its bioactivities. However, the role of LF iron saturation in protecting infant intestinal inflammation has not been clearly clarified. Therefore, in this study, young mice models with intestinal damage induced by lipopolysaccharides (LPS) in vivo and primary intestinal epithelial cells in vitro were constructed to enteritis injury in infants for investigation. The apo-LF and holo-LF were subsequently applied to the mouse models to investigate and compare their levels of protection in the intestinal inflammatory injury, as well as to identify which LF was most active. Moreover, the specific mechanism of the LF with optimal iron saturation was further investigated through Western blot assay. Results demonstrated that disease activity index, shortened length of colon tissue, and histopathological score were significantly decreased in the apo-LF group compared with those of the LPS group and the holo-LF group. In the apo-LF group, the concentration of LPS in the intestinal tract and the number of gramnegative bacteria colonies decreased significantly and the expression levels of proinflammatory factors in the colon tissue were downregulated, in comparison with those in the LPS group. The findings of this study thus verify that apo-LF can significantly alleviate enteritis injury caused by LPS, through regulating the PPAR-γ/ PFKFB3/NF-κB inflammatory pathway.

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“… 1 , 2 Inflammation has been defined as a complex biological response of vascular tissues to different types of harmful stimuli, 3 , 4 such as damaged cells, irritants, and pathogens. Inflammation has also been linked to the release of proinflammatory cytokines, 5 , 6 12- O -tetradecanoylphorbol-13-acetate (TPA) is a well-known inducer of inflammatory, 7 , 8 and the signal transduction pathways such as MAPK, p65, and I-κB kinase (IKK) activate proinflammatory transcription factors including NF-κB, activator protein 1 (AP-1), and cAMP response element-binding protein. 9 , 10 These transcription factors are critically involved in the expression of various proinflammatory genes, 11 – 14 including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2), all of which could be a sign of many diseases.…”

Section: Introductionmentioning

confidence: 99%

The biological evaluation of fusidic acid and its hydrogenation derivative as antimicrobial and anti-inflammatory agents

Wu¹,

He²,

Hong³

et al. 2018

IDR

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BackgroundFusidic acid (FA) (WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria.MethodsHerein, the hydrogenation derivative (WU-FA-01) of FA was prepared and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammatory properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model.ResultsThe results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 displayed a high level of antimicrobial activity against Gram-positive strains. Moreover, killing kinetic studies were performed and the results were in accordance with the minimum inhibitory concentration and minimum bactericidal concentration results. We also demonstrated that the topical application of WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a dose-dependent manner. This inhibitory effect was associated with the inhibition of TPA-induced upregulation of proinflammatory cytokines IL-1β, TNF-α, and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α in the TPA-induced mouse ear model.ConclusionOverall, our results showed that WU-FA-00 and WU-FA-01 not only had effective antimicrobial activities in vitro, especially to the Gram-positive bacteria, but also possessed strong anti-inflammatory effects in vivo. These results provide a scientific basis for developing FA derivatives as antimicrobial and anti-inflammatory agents.

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Endocytosis of pro-inflammatory cytokine receptors and its relevance for signal transduction

Cited by 11 publications

References 97 publications

Identification of Common Differentially Expressed Genes and Potential Therapeutic Targets in Ulcerative Colitis and Rheumatoid Arthritis

Identification of Common Differentially Expressed Genes and Potential Therapeutic Targets in Ulcerative Colitis and Rheumatoid Arthritis

Protective effects of recombinant lactoferrin with different iron saturations on enteritis injury in young mice

The biological evaluation of fusidic acid and its hydrogenation derivative as antimicrobial and anti-inflammatory agents

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