Exclusive inhibition of IL-6 trans-signaling by soluble gp130FlyRFc

Berg, Anna F.; Ettich, Julia; Weitz, Hendrik T.; Krusche, Matthias; Floß, Doreen M.; Scheller, Jürgen; Moll, Jens M.

doi:10.1016/j.cytox.2021.100058

Cited by 13 publications

(12 citation statements)

References 37 publications

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“…Similarly, IL-6 was selected as a representative anti-inflammatory target for molecular docking in this study because of its importance in inflammation. Site I in IL-6 is the binding domain of IL-6R and is closely associated with classic signaling pathways [ 21 , 22 ]. Therefore, a grid box (126 Å × 126 Å × 114 Å, 0.375 Å spacing) was constructed around site I and centered at the following coordinates: x = 1.301, y = −19.932, z = 8.838.…”

Section: Resultsmentioning

confidence: 99%

Spectrum-Effect Relationship-Based Strategy Combined with Molecular Docking to Explore Bioactive Flavonoids from Sceptridium ternatum

et al. 2022

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Sceptridium ternatum is a herbaceous plant with significant potential for pharmaceutical and cosmetic applications. In this study, we established a spectrum-effect relationship-based strategy to investigate the bioactive basis and tissue distribution in S. ternatum. First, a phytochemical analysis on the ethanol extracts from roots, stems, and leaves of S. ternatum was performed using the colorimetric method, high-performance liquid chromatography–ultraviolet (HPLC–UV), and high-performance liquid chromatography–electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC–ESI-Q-TOF-MS/MS). Then, radical scavenging assays and the lipopolysaccharide-stimulated RAW 264.7 cell model were used to estimate the antioxidant and anti-inflammatory activities, respectively. Spectrum-effect relationship analysis and molecular docking were further employed to evaluate the correlation between the phytochemical profile and anti-inflammatory activity. Our results demonstrate that S. ternatum leaves contained the most abundant flavonoids and exerted the best biological activities. Their IC50 values for scavenging 2,2ʹ-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl radicals were 2.43 ± 0.13 and 5.36 ± 0.54 mg/mL, respectively. In lipopolysaccharide-stimulated RAW 264.7 cells, the leaf extract caused the greatest reduction in nitric oxide production (38.15%) and interleukin-6 release (110.86%). Spectrum-effect relationship analysis and molecular docking indicated that quercetin 3-O-rhamnoside-7-O-glucoside possessed high anti-inflammatory activity by binding with interleukin-6. In conclusion, S. ternatum is a rich source of bioactive flavonoids with potential for exploitation in the prevention and treatment of oxidative stress and inflammation-related pathologies.

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Section: Resultsmentioning

confidence: 99%

Spectrum-Effect Relationship-Based Strategy Combined with Molecular Docking to Explore Bioactive Flavonoids from Sceptridium ternatum

et al. 2022

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“…The studies by Gross et al demonstrated that serum concentrations of IL6 in patients with in ammatory bowel disease, as compared to healthy controls, increased signi cantly [30] . Further study found that high expression of IL6 was common in patients with Crohn's disease and ulcerative colitis and closely associated with disease activities [31] . Louis et al have used high IL6 serum levels as the biomarkers to predict for stopping recurrence in patients with Crohn's disease [32,33] .…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of potential key genes and pathways in neonatal necrotizing enterocolitis

Liu

Zhang

et al. 2022

Preprint

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Objective To detect differentially expressed genes in patients with neonatal necrotizing enterocolitis (NEC) by bioinformatics methods and to provide new ideas and research directions for the prevention, early diagnosis and treatment of NEC. Methods Gene chip data were downloaded from the Gene Expression Omnibus database. The genes that were differentially expressed in NEC compared with normal intestinal tissues were screened with GEO2R. The functions, pathway enrichment and protein interactions of these genes were analyzed with DAVID and STRING. Then, the core network genes and significant protein interaction modules were detected using Cytoscape software. Results Overall, a total of 236 differentially expressed genes were detected, including 225 upregulated genes and 11 downregulated genes, and GO and KEGG enrichment analyses were performed. The results indicated that the upregulated differentially expressed genes were related to the dimerization activity of proteins, while the downregulated differentially expressed genes were related to the activity of cholesterol transporters. KEGG enrichment analysis revealed that the differentially expressed genes were significantly concentrated in metabolism and fat digestion and absorption pathways. Through STRING analysis, 9 key genes in the protein network interaction map were identified: EPCAM, CDH1, CFTR, IL-6, APOB, APOC3, APOA4, SLC2A and NR1H4. Conclusion Metabolic pathways and biological processes may play important roles in the development of NEC. The screening of possible core targets by bioinformatics is helpful in clarifying the pathogenesis of NEC at the gene level and in providing references for further research.

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“…Studies by Gross et al demonstrated that serum concentrations of IL6 in patients with inflammatory bowel disease, compared to healthy controls, increased significantly [ 30 ]. Further study found that high expression of IL6 was common in patients with Crohn's disease and ulcerative colitis and was closely associated with disease activities [ 31 ]. Louis et al used high IL6 serum levels as biomarkers to predict recurrence cessation in patients with Crohn’s disease [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of potential key genes and pathways in neonatal necrotizing enterocolitis

Liu

Zhang

et al. 2022

BMC Pediatr

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Objective To detect differentially expressed genes in patients with neonatal necrotizing enterocolitis (NEC) by bioinformatics methods and to provide new ideas and research directions for the prevention, early diagnosis and treatment of NEC. Methods Gene chip data were downloaded from the Gene Expression Omnibus database. The genes that were differentially expressed in NEC compared with normal intestinal tissues were screened with GEO2R. The functions, pathway enrichment and protein interactions of these genes were analyzed with DAVID and STRING. Then, the core network genes and significant protein interaction modules were detected using Cytoscape software. Results Overall, a total of 236 differentially expressed genes were detected, including 225 upregulated genes and 11 downregulated genes, and GO and KEGG enrichment analyses were performed. The results indicated that the upregulated differentially expressed genes were related to the dimerization activity of proteins, while the downregulated differentially expressed genes were related to the activity of cholesterol transporters. KEGG enrichment analysis revealed that the differentially expressed genes were significantly concentrated in metabolism, fat digestion and absorption pathways. Through STRING analysis, 9 key genes in the protein network interaction map were identified: EPCAM, CDH1, CFTR, IL-6, APOB, APOC3, APOA4, SLC2A and NR1H4. Conclusion Metabolic pathways and biological processes may play important roles in the development of NEC. The screening of possible core targets by bioinformatics is helpful in clarifying the pathogenesis of NEC at the gene level and in providing references for further research.

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Exclusive inhibition of IL-6 trans-signaling by soluble gp130FlyRFc

Abstract: Highlights A variety of sgp130Fc muteins was generated. Introduction of a gp130 SNP (R281Q) into sgp130Fc increases IL-6 specificity. The sgp130Fc variant sgp130 FlyR exclusively affects IL-6 trans-signaling.

Cited by 13 publications

References 37 publications

Spectrum-Effect Relationship-Based Strategy Combined with Molecular Docking to Explore Bioactive Flavonoids from Sceptridium ternatum

Spectrum-Effect Relationship-Based Strategy Combined with Molecular Docking to Explore Bioactive Flavonoids from Sceptridium ternatum

Bioinformatics analysis of potential key genes and pathways in neonatal necrotizing enterocolitis

Bioinformatics analysis of potential key genes and pathways in neonatal necrotizing enterocolitis

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