scholarly journals Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis patients

2011 ◽  
Vol 71 (1) ◽  
pp. 150-154 ◽  
Author(s):  
M Chemel ◽  
B Le Goff ◽  
R Brion ◽  
C Cozic ◽  
M Berreur ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Messenger Rna ◽  
Synovial Fibroblasts ◽  
Total Leucocyte Count ◽  
Dependent Manner ◽  
Jnk Pathway ◽  
Dose Time ◽  
Downstream Effector ◽  
Factor Α

ObjectivesInterleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA).MethodsImmunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor α (TNFα) and IL-1β. Wild-type, jnk1−/−–jnk2−/− and nemo−/− murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-κB) and JNK in that effect.ResultsIL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNFα and IL-1β stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-κB and JNK pathway.ConclusionThis work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNFα and IL-1β, may contribute to inflammation and bone erosions in RA.

Expression and Function of Histone Deacetylases in Rheumatoid Arthritis Synovial Fibroblasts

2009 ◽  
Vol 36 (8) ◽  
pp. 1580-1589 ◽  
Author(s):  
MARIKA HORIUCHI ◽  
AKIO MORINOBU ◽  
TAKAAKI CHIN ◽  
YOSHITADA SAKAI ◽  
MASAHIRO KUROSAKA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Histone Deacetylases ◽  
Messenger Rna ◽  
Hdac Inhibitors ◽  
Annexin V ◽  
Synovial Fibroblasts ◽  
Chain Reactions ◽  
Cell Counts ◽  
Factor Α

Objective.To explore the effects of histone deacetylases (HDAC) on rheumatoid arthritis synovial fibroblasts (RA-SF).Methods.The expression of mRNA encoding HDAC1 through HDAC11 in RA-SF and osteoarthritis-SF (OA-SF) was determined using real-time polymerase chain reactions. The functions of HDAC1 and HDAC2 in RA-SF were assessed using small interfering RNA (siRNA) technology. Cell counts and proliferation were examined by MTT assays and BrDU ELISA, respectively, and apoptosis was determined using the TUNEL assay and annexin V staining. Levels of cell cycle-related molecules and matrix metalloproteinases (MMP) were tested by Western blotting and ELISA, respectively.Results.Messenger RNA expression of HDAC1 was significantly higher in RA-SF than in OA-SF. Knockdown of HDAC1 and HDAC2 by siRNA resulted in decreased cell counts and cell proliferation, and increased apoptosis in RA-SF. Expression of p16, p21, and p53 was increased by knockdown of both HDAC1 and HDAC2. On the other hand, knockdown of HDAC1, but not of HDAC2, upregulated tumor necrosis factor-α-induced MMP-1 production by RA-SF.Conclusion.HDAC1 is overexpressed in RA-SF compared to OA-SF. HDAC1 supports cell proliferation and survival of RA-SF, but suppresses MMP-1 production. HDAC2 also plays an important role in cell proliferation and apoptosis of RA-SF. Our study provides useful information to develop new HDAC inhibitors for the treatment of RA.

scholarly journals Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis

2006 ◽  
Vol 203 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Tetsuya Honda ◽  
Eri Segi-Nishida ◽  
Yoshiki Miyachi ◽  
Shuh Narumiya
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
The Other ◽  
Receptor Subtype ◽  
Significant Suppression ◽  
Wild Type ◽  
Collagen Induced Arthritis

Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP−/−) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP−/− mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.

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

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Sheng-Mou Hou ◽  
Po-Chun Chen ◽  
Chieh-Mo Lin ◽  
Mei-Ling Fang ◽  
Miao-Ching Chi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Chemical Inhibitors ◽  
Shrna Plasmid ◽  
Signal Cascades

Abstract 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 the 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 were 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.

scholarly journals Relationship between α1-antitrypsin inactivation and tumor necrosis factor α concentration in the synovial fluid of patients with rheumatoid arthritis

1994 ◽  
Vol 37 (12) ◽  
pp. 1723-1726 ◽  
Author(s):  
Keith Chidwick ◽  
Catherine E. Whichelow ◽  
Zhi Zhang ◽  
Kevin Fairburn ◽  
John A. Sachs ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Synovial Fluid ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Soluble LILRA3, a Potential Natural Antiinflammatory Protein, Is Increased in Patients with Rheumatoid Arthritis and Is Tightly Regulated by Interleukin 10, Tumor Necrosis Factor-α, and Interferon-γ

2010 ◽  
Vol 37 (8) ◽  
pp. 1596-1606 ◽  
Author(s):  
HONGYAN AN ◽  
VASUDHA CHANDRA ◽  
BARBARA PIRAINO ◽  
LUIS BORGES ◽  
CAROLYN GECZY ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Synovial Fluid ◽  
Protein Expression ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Factor Α ◽  
Necrosis Factor

Objective.Leukocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of cell-surface receptors with inhibitory or activating functions. LILRA3 lacks transmembrane and cytoplasmic domains, suggesting that it may be secreted. LILRA3 has high homology to activating LILRA1 and A2, hence may act as a soluble agonist/antagonist to these receptors. Individuals lacking the LILRA3 gene have higher incidence of multiple sclerosis and Sjögren’s syndrome, suggesting LILRA3 may be antiinflammatory. LILRA3 mRNA was detected in monocytes and mast cells but no protein expression has ever been described. Our aim was to examine LILRA3 protein expression in serum and synovial fluid of patients with rheumatoid arthritis (RA) and determine its in vitro regulation.Methods.We developed a new ELISA to examine levels of LILRA3 in serum, synovial fluid, and/or culture supernatants from controls and patients with RA, degenerative arthritis, or gout. We used qRT-PCR and flow cytometry to determine the expression and cytokine-mediated regulation of LILRA3.Results.LILRA3 protein is constitutively present in normal serum, with significantly higher concentrations in patients with RA. Serum LILRA3 concentrations from RA patients correlated with disease activity and levels in synovial fluid. Treatment of monocytes with interleukin 10 or interferon-γ significantly upregulated while tumor necrosis factor-α significantly downregulated LILRA3 mRNA and protein expression.Conclusion.We show for the first time that LILRA3 is significantly increased in serum of patients with RA and is tightly regulated by key cytokines involved in pathogenesis of RA. These results suggest that LILRA3 may play a role in chronic inflammatory conditions such as RA.

Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis

2017 ◽  
Vol 45 (4) ◽  
pp. 563-573 ◽  
Author(s):  
Ngar-Woon Kam ◽  
Dehua Liu ◽  
Zhe Cai ◽  
Wah-Yan Mak ◽  
Chun-Kwok Wong ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Synovial Fibroblasts ◽  
B Cell Activation ◽  
Qrt Pcr ◽  
Tnf Α ◽  
Factor Α

Objective.Elevated expression of interleukin 35 (IL-35) is associated with autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the functional interaction among IL-35, B cells, and stromal cells residing in the synovium of patients with RA and osteoarthritis (OA).Methods.IL-35 (EBI-3/p35) expression was investigated in RA and OA synovium using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. IL-35 receptor (IL-35R) expression on B cells dissociated from synovium and periphery of patients with RA, OA, and healthy donor controls (HC) was determined by flow cytometry. The degree of B cells activation after IL-4 and/or IL-35 stimulation was measured by flow cytometry and qRT-PCR. Synovial fibroblasts (SF) purified from RA and OA synovium were cocultured with peripheral HC B cells in the presence/absence of tumor necrosis factor-α (TNF-α) and with/without anti-IL-35–blocking antibodies.Results.EBI-3/p35 transcripts were expressed in close proximity to B cells residing in RA and OA synovium. IL-35R subunits, gp130 and IL-27Rα, but not IL-12Rβ2, were expressed in B cells extracted from the synovium and periphery of patients with RA/OA. Notably, RA synovium expressed the highest level of IL-27Rα on their cell surface. IL-35 induced proliferation and IgG production in HC B cells. Cocultures of HC B cells with RASF, but not OASF, exhibited significantly elevated B cells activation. TNF-α–induced, RASF-dependent secretion of IgG in B cells is partly IL-35–dependent.Conclusion.To our knowledge, for the first time we demonstrated that synovial/peripheral B cells expressed IL-35R and were responsive to IL-35 stimulation. SF residing in RA synovium can be linked to B cell activation and maintenance in RA synovium through IL-35.

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

2020 ◽  
Author(s):  
Sheng-Mou Hou ◽  
PoChun Chen ◽  
Chieh-Mo Lin ◽  
Mei-Ling Fang ◽  
Miao-Ching Chi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Proinflammatory Cytokine ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Synovial Fibroblasts ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Chemical Inhibitors ◽  
Shrna Plasmid ◽  
Signal Cascades

Abstract 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.

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