Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What’s the Difference?

Avcı, Ali; Feist, Eugen; Burmester, Gerd R

doi:10.1007/s40259-018-0320-3

Cited by 50 publications

(39 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Sirukumab, ein weiterer IL-6-Blocker, zeigte gute klinische Wirksamkeit in klinischen Prüfungen, allerdings kam es zu erhöhter Mortalität nach Open-label-Studien, woraufhin die regulatorischen Behörden keine Zulassung erteilten und weitere Sicherheitsdaten verlangten [44].…”

Section: Introductionunclassified

Biologika und „small molecules“ bei der rheumatoiden Arthritis

Blüml

2020

Z Rheumatol

View full text Add to dashboard Cite

ZusammenfassungDie Therapie der rheumatoiden Arthritis hat in den letzten Jahren gewaltige Umbrüche erfahren. Es steht mittlerweile ein großes Armamentarium an verschiedensten Medikamenten mit unterschiedlichen molekularen Angriffspunkten zur Verfügung. Zu diesen neuen Waffen zählen die Biologika (biologische DMARDs [bDMARDs; „disease modifying antirheumatic drugs“]) und die „targeted synthetic DMARDs“ (tsDMARDs). Gemeinsam ist diesen neueren Therapien für die rheumatoide Arthritis, dass man im Unterschied zu den konventionellen DMARDs die molekularen Angriffspunkte kennt. Mithilfe der neuen Medikamente kann den meisten Patienten geholfen werden, obwohl es nach wie vor Patienten gibt, die auf alle vorhandenen Therapien nicht adäquat reagieren. In diesem Review soll ein kurzer Überblick über die derzeitig verfügbaren und wirksamen Präparate für die Behandlung der rheumatoiden Arthritis gegeben werden.

show abstract

Section: Introductionunclassified

Biologika und „small molecules“ bei der rheumatoiden Arthritis

Blüml

2020

Z Rheumatol

View full text Add to dashboard Cite

show abstract

“…Dysregulation of IL-6 leads to many autoimmune and in ammatory diseases, including RA (43). Targeting IL-6 with the anti-IL-6 receptor (IL-6R) antibody tocilizumab is effective for treating RA (44). A previous review has con rmed the important role of IL-6 in OA progression (45), which is supported by the nding that IL-6 expression is elevated in OA human synovial uid and sera (46).…”

Section: Discussionmentioning

confidence: 97%

CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK and AP-1 pathway

Hou

Chen

Lin

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well-characterized in RA progression, but less so in OA pathogenesis. Methods: The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs and shRNAs. Results: Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf and MAPKs was found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs. Conclusions: Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.

show abstract

“…Ectopic expression of p16 INK4A protein can also suppress LPS-induced IL-6 expression in macrophages [38] , and simultaneously enhance the observations that CDK inhibitory proteins relative features to counteract in ammation [39] . Interleukin-6 (IL-6) signaling is a critical target in in ammatory pathways [40] . In patients with RA, the high level of IL-6 and IL-6R are found in both serum and synovial uid of related joints effected by the disease.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes and signaling pathways in rheumatoid arthritis by integrated bioinformatics analysis

Zhou

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background The disability rate associated with rheumatoid arthritis (RA) ranks high among inflammatory joint diseases. However, the cause and potential molecular events are as yet not clear. Here, we aimed to identify key genes and pathways involved in RA utilizing integrated bioinformatics analysis and uncover underlying molecular mechanisms. Materials and methods The expression profiles of GSE55235, GSE55457, GSE55584 and GSE77298 were downloaded from the Gene Expression Omnibus database, which contained 76 synovial membrane samples, including 49 RA samples and 27 controls. The microarray datasets were consolidated and differentially expressed genes (DEGs) were acquired and further analyzed by bioinformatics techniques. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using R (version 3.6.1), respectively. The protein-protein interaction (PPI) networks of DEGs were developed utilizing the STRING database. Results A total of 828 DEGs were recognized, with 758 up-regulated and 70 down-regulated. GO and KEGG pathway analyses demonstrated that these DEGs focused primarily on multifactorial binding, transcription activity, cytokin-cytokin receptor interaction and relevant signaling pathways. The 30 most firmly related genes among DEGs were identified from the PPI network. Conclusion This study shows that screening for DEGs and pathways utilizing integrated bioinformatics analyses could aid in the comprehension of the molecular mechanisms involved in RA development. In addition, our study provides valuable data for the effective prevention, diagnosis, treatment and rehabilitation of RA patients as well as providing potential targets for the treatment of RA.

show abstract

Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What’s the Difference?

Cited by 50 publications

References 102 publications

Biologika und „small molecules“ bei der rheumatoiden Arthritis

Biologika und „small molecules“ bei der rheumatoiden Arthritis

CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK and AP-1 pathway

Identification of differentially expressed genes and signaling pathways in rheumatoid arthritis by integrated bioinformatics analysis

Contact Info

Product

Resources

About