IL6/sIL6R regulates TNFα-inflammatory response in synovial fibroblasts through modulation of transcriptional and post-transcriptional mechanisms

Autor: Alvaro Valin, Manuel J. Del Rey, Cristina Municio, Alicia Usategui, Marina Romero, Jesús Fernández-Felipe, Juan D. Cañete, Francisco J. Blanco, Yolanda Ruano, Gabriel Criado, José L. Pablos
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: BMC Molecular and Cell Biology, Vol 21, Iss 1, Pp 1-12 (2020)
Druh dokumentu: article
ISSN: 2661-8850
DOI: 10.1186/s12860-020-00317-7
Popis: Abstract Introduction The clinical efficacy of specific interleukin-6 inhibitors has confirmed the central role of IL6 in rheumatoid arthritis (RA). However the local role of IL6, in particular in synovial fibroblasts (SF) as a direct cellular target to IL6/sIL6R signal is not well characterized. The purpose of the study was to characterize the crosstalk between TNFα and IL6/sIL6R signaling to the effector pro-inflammatory response of SF. Methods SF lines were stimulated with either TNFα, IL6/sIL6R, or both together, for the time and dose indicated for each experiment, and where indicated, cells were treated with inhibitors actinomycin D, adalimumab, ruxolitinib and cycloheximide. mRNA expression of cytokines, chemokines and matrix metalloproteases (MMPs) were analyzed by quantitative RT-PCR. Level of IL8/CXCL8 and CCL8 in culture supernatants was measured by ELISA. Mononuclear and polymorphonuclear cells migration assays were assessed by transwell using conditioned medium from SF cultures. Statistical analyses were performed as indicated in the corresponding figure legends and a p-value
Databáze: Directory of Open Access Journals
Nepřihlášeným uživatelům se plný text nezobrazuje