Morphofunctional analysis of fibroblast-like synoviocytes in human rheumatoid arthritis and mouse collagen-induced arthritis

Advances in Rheumatology

Research

Gustavo Gomes Resende¹  Ricardo Machado Xavier²  Marcus Vinicius Melo de Andrade³  Camilla Ribeiro Lima Machado³  Felipe Ferraz Dias⁴  Patrícia Gnieslaw de Oliveira⁵  Adriana Maria Kakehasi⁶ 

[1] Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Internal Medicine Department, Faculty of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;Laboratory of Scientific Research - Professor Lineu Freire-Maia, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Laboratory of Scientific Research, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;Medicine Department, University of California of San Diego, San Diego, USA;Post Graduate Program in Sciences Applied to Adult Health Care, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil;

关键词: Fibroblast-like synoviocytes;    Rheumatoid arthritis;    Collagen-induced arthritis;    Signaling transduction;    Interleukin-6;    Metalloproteinases;    Electronic microscopy;   

DOI  :  10.1186/s42358-022-00281-0

 received in 2022-07-15, accepted in 2022-11-28,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundFibroblast-like synoviocytes (FLS) play a prominent role in rheumatoid synovitis and degradation of the extracellular matrix through the production of inflammatory cytokines and metalloproteinases (MMPs). Since animal models are frequently used for elucidating the disease mechanism and therapeutic development, it is relevant to study the ultrastructural characteristics and functional responses in human and mouse FLS. The objective of the study was to analyze ultrastructural characteristics, Interleukin-6 (IL-6) and Metalloproteinase-3 (MMP-3) production and the activation of intracellular pathways in Fibroblast like synoviocytes (FLS) cultures obtained from patients with rheumatoid arthritis (RA) and from mice with collagen-induced arthritis (CIA).MethodsFLSs were obtained from RA patients (RA-FLSs) (n = 8) and mice with CIA (CIA-FLSs) (n = 4). Morphology was assessed by transmission and scanning electron microscopy. IL-6 and MMP-3 production was measured by ELISA, and activation of intracellular signaling pathways (NF-κB and MAPK: p-ERK1/2, p-P38 and p-JNK) was measured by Western blotting in cultures of RA-FLSs and CIA-FLSs stimulated with tumor necrosis factor-alpha (TNF-α) and IL-1β.ResultsRA-FLS and CIA-FLS cultures exhibited rich cytoplasm, rough endoplasmic reticula and prominent and well-developed Golgi complexes. Transmission electron microscopy demonstrated the presence of lamellar bodies, which are cytoplasmic structures related to surfactant production, in FLSs from both sources. Increased levels of pinocytosis and numbers of pinocytotic vesicles were observed in RA-FLSs (p < 0.05). Basal production of MMP-3 and IL-6 was present in RA-FLSs and CIA-FLSs. Regarding the production of MMP-3 and IL-6 and the activation of signaling pathways, the present study demonstrated a lower response to IL-1β by CIA-FLSs than by RA-FLSs.ConclusionThis study provides a comprehensive understanding of the biology of RA-FLS and CIA-FLS. The differences and similarities in ultrastructural morphology and important inflammatory cytokines shown, contribute to future in vitro studies using RA-FLS and CIA-FLS, in addition, they indicate that the adoption of CIA-FLS for studies should take careful and be well designed, since they do not completely resemble human diseases.

【 授权许可】

CC BY   
© The Author(s) 2022

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