Interleukin-6 in Rheumatoid Arthritis

Pandolfi, Franco; Franza, Laura; Carusi, Valentina; Altamura, Simona; Andriollo, Gloria; Nucera, Eleonora

doi:10.3390/ijms21155238

Cited by 116 publications

(97 citation statements)

References 89 publications

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“…IL-6, together with IL-27, belongs to a broader group of cytokines, which can act in a pro-and anti-inflammatory manner [ 92 , 93 ] mediating lipid and iron metabolism, regulating overall levels of organisms’ fatigue and pain, stimulating angiogenesis and disease progression [ 94 , 95 ]. In RA development and course, IL-6 seems to be another pivotal cytokine and is already targeted in various therapies [ 96 ].…”

Section: Ra Markers and Most Common Cytokines—potential Therapeutic Targetsmentioning

confidence: 99%

“…In addition, IL-6 can enhance pannus formation by increasing VEGF expression [ 49 ]. Furthermore, IL-6 is involved in increasing oxidative stress [ 49 ], promoting mononuclear cell infiltration [ 92 ], and activation of lymphocytes [ 96 ]. Activated B cells differentiate into plasma cells and increase antibody levels, whose production and class switching may also be affected by this cytokine [ 93 ].…”

Section: Ra Markers and Most Common Cytokines—potential Therapeutic Targetsmentioning

confidence: 99%

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The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis

2021

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Rheumatoid arthritis (RA) is a widespread chronic autoimmune disorder affecting the joints, causing irreversible cartilage, synovium, and bone degradation. During the course of the disease, many immune and joint cells are activated, causing inflammation. Immune cells including macrophages, lymphocytes, neutrophils, mast cells, natural killer cells, innate lymphoid cells, as well as synovial tissue cells, like fibroblast-like synoviocytes, chondrocytes, and osteoclasts secrete different proinflammatory factors, including many cytokines, angiogenesis-stimulating molecules and others. Recent studies reveal that curcumin, a natural dietary anti-inflammatory compound, can modulate the response of the cells engaging in RA course. This review comprises detailed data about the pathogenesis and inflammation process in rheumatoid arthritis and demonstrates scientific investigations about the molecular interactions between curcumin and immune cells responsible for rheumatoid arthritis development to discuss this herbal drug’s immunoregulatory role in RA treatment.

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Section: Ra Markers and Most Common Cytokines—potential Therapeutic Targetsmentioning

confidence: 99%

Section: Ra Markers and Most Common Cytokines—potential Therapeutic Targetsmentioning

confidence: 99%

The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis

2021

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“…In addition, we analyzed the importance prioritization (adjacent nodes count of each protein) of proteins according to the network, and the leading 30 genes with higher connection were visualized by constructing a bar plot diagram ( Figure 6 ), which indicates the 30 genes or proteins that may play a bridge role in connecting other nodes in the PPI network. These 30 genes or proteins include inflammation-associated genes (IL6 [ 36 ], NFKBIA [ 37 ]), cell proliferation-, differentiation-, and transformation-related genes (FOS [ 38 ], EGFR [ 39 ], MAPK8 [ 40 ], NR3C1 [ 41 ], RHOA [ 42 ], and PARP1 [ 43 ]), cell apoptosis-related genes (CASP3, CASP8 [ 44 ], CASP9 [ 45 ], MYC [ 46 ], CYCS [ 47 ], HIF1A [ 48 ], MCL1 [ 49 ], and GSK3B [ 50 ]), cell cycle-related gene (CCND1 [ 51 ]), hormone-related genes (INS [ 52 ], ESR1 [ 53 ], AR [ 54 ], and PGR [ 55 ]), angiogenesis-related gene (VEGFA [ 56 ]), and transcription factor (RELA [ 57 ]).…”

Section: Resultsmentioning

confidence: 99%

Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

Tang

Xie

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the main components and unravel the potential mechanism of simiao pill (SM) on rheumatoid arthritis (RA) based on network pharmacological analysis and molecular docking. Methods. Related compounds were obtained from TCMSP and BATMAN-TCM database. Oral bioavailability and drug-likeness were then screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Additionally, target genes related to RA were acquired from GeneCards and OMIM database. Correlations about SM-RA, compounds-targets, and pathways-targets-compounds were visualized through Cytoscape 3.7.1. The protein-protein interaction (PPI) network was constructed by STRING. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed via R packages. Molecular docking analysis was constructed by the Molecular Operating Environment (MOE). Results. A total of 72 potential compounds and 77 associated targets of SM were identified. The compounds-targets network analysis indicated that the 6 compounds, including quercetin, kaempferol, baicalein, wogonin, beta-sitosterol, and eugenol, were linked to ≥10 target genes, and the 10 target genes (PTGS1, ESR1, AR, PGR, CHRM3, PPARG, CHRM2, BCL2, CASP3, and RELA) were core target genes in the network. Enrichment analysis indicated that PI3K-Akt, TNF, and IL-17 signaling pathway may be a critical signaling pathway in the network pharmacology. Molecular docking showed that quercetin, kaempferol, baicalein, and wogonin have good binding activity with IL6, VEGFA, EGFR, and NFKBIA targets. Conclusion. The integrative investigation based on bioinformatics/network topology strategy may elaborate on the multicomponent synergy mechanisms of SM against RA and provide the way out to develop new combination medicines for RA.

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“…This microenvironment promotes Th17 differentiation to the detriment of T regulators (Treg) differentiation. To complete the loop, IL-1, IL-6, IL-17, and TNF-α are known to stimulate osteoclastogenesis, which results in the degradation of mineralized tissue such as mineralized cartilage and subchondral bone [ 81 , 82 , 83 ]. Similar to what is observed in OA, leptin serum levels are higher in RA patients, so that overweight and obesity have been associated with RA [ 84 , 85 ].…”

Section: Overview Of the Most Frequent Osteoimmunological Disordermentioning

confidence: 99%

Breast Cancer and Microcalcifications: An Osteoimmunological Disorder?

Clemenceau

Michou

Diorio

et al. 2020

IJMS

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The presence of microcalcifications in the breast microenvironment, combined with the growing evidences of the possible presence of osteoblast-like or osteoclast-like cells in the breast, suggest the existence of active processes of calcification in the breast tissue during a woman’s life. Furthermore, much evidence that osteoimmunological disorders, such as osteoarthritis, rheumatoid arthritis, or periodontitis influence the risk of developing breast cancer in women exists and vice versa. Antiresorptive drugs benefits on breast cancer incidence and progression have been reported in the past decades. More recently, biological agents targeting pro-inflammatory cytokines used against rheumatoid arthritis also demonstrated benefits against breast cancer cell lines proliferation, viability, and migratory abilities, both in vitro and in vivo in xenografted mice. Hence, it is tempting to hypothesize that breast carcinogenesis should be considered as a potential osteoimmunological disorder. In this review, we compare microenvironments and molecular characteristics in the most frequent osteoimmunological disorders with major events occurring in a woman’s breast during her lifetime. We also highlight what the use of bone anabolic drugs, antiresorptive, and biological agents targeting pro-inflammatory cytokines against breast cancer can teach us.

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Interleukin-6 in Rheumatoid Arthritis

Cited by 116 publications

References 89 publications

The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis

The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis

Integrating Network Pharmacology with Molecular Docking to Unravel the Active Compounds and Potential Mechanism of Simiao Pill Treating Rheumatoid Arthritis

Breast Cancer and Microcalcifications: An Osteoimmunological Disorder?

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