Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5

Abstract

ObjectivesThe main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells, an important source of cytokines and chemokines, which are associated with inflammation. The aim of this study was to evaluate gene expression in the microdissected synovial lining cells of RA patients, using those of osteoarthritis (OA) patients as the control.MethodsSamples were obtained during total joint replacement from 11 RA and five OA patients. Total RNA from the synovial lining cells was derived from selected specimens by laser microdissection (LMD) for subsequent cDNA microarray analysis. In addition, the expression of significant genes was confirmed immunohistochemically.ResultsThe 14 519 genes detected by cDNA microarray were used to compare gene expression levels in synovial lining cells from RA with those from OA patients. Cluster analysis indicated that RA cells, including low- and high-expression subgroups, and OA cells were stored in two main clusters. The molecular activity of RA was statistically consistent with its clinical and histological activity. Expression levels of signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and the chemokines CXCL9, CXCL10, and CCL5 were statistically significantly higher in the synovium of RA than in that of OA. Immunohistochemically, the lining synovium of RA, but not that of OA, clearly expressed STAT1, IRF1, and chemokines, as was seen in microarray analysis combined with LMD.ConclusionsOur findings indicate an important role for lining synovial cells in the inflammatory and proliferative processes of RA. Further understanding of the local signalling in structural components is important in rheumatology.

Increased production of circulating soluble co-stimulatory molecules CTLA-4, CD28 and CD80 in patients with rheumatoid arthritis

“…Indeed, there was significant elevation of concentrations of serum pro-inflammatory cytokines (IL-1β, IL-6, IL-18, IL-17, IL-27) [2,33,34], and chemokines (CXCL8, CXCL9, CXCL10, and CCL5) [35]. In addition, anomalous activation of various signaling axes including various MAPK, AKT, NFkappaB, Bcl-2 family members, and JAK/STAT has been suggested to affect multiple molecular processes in RA [36], and these signaling pathways may involve in the aberrant production of sCTLA-4, sCD28 and sCD80 in RA patients.…”

Gene selection and dynamic neutrosophic cognitive map with bat algorithm (DNCM-BA) for diagnose of rheumatoid arthritis (RAs)

“…RA patients having low levels of TNF-α expression, who as well containing the expression of other genes at the degree of strong subjects, must be stratified into a diverse subset needing particular treatment that may include targets except pro-inflammatory cytokine signaling paths. Yoshida et al [20] assessed gene expression in the micro-dissected synovial lining cells of RA patients, by means of those of Osteoarthritis (OA) patients as the control. The molecular activity of RA was reliable with its medical as well as histological activity.…”

The signal transducer and activator of transcription factors lodge in immunopathogenesis of rheumatoid arthritis

“…De Hooge et al reported that zymosan-induced arthritis in STAT1-deficient mice is associated with increased joint inflammation and formation of granuloma (74). Yoshida et al using microarray analysis in 16 patients (11 patients with RA and 9 with osteoarthritis (OA) suggested that the expression levels of STAT1 were significantly higher in RA synovium compared to OA (86) reported that arthritis severity in mice appeared to be regulated by IL-4 through a STAT6 dependent mechanism (93). In IL-4 or STAT6 deficient mice, they observed a more severe and progressive arthritis suggesting IL-4 mediates anti-inflammatory reaction through STAT6 (93).…”