Different expression levels of TNF receptors on the rheumatoid synovial macrophages derived from surgery and a synovectomy as detected by a new flow cytometric analysis

Ida, Hiroaki; Aramaki, Toshiyuki; Nakamura, Hideki; Fujikawa, Keita; Arima, Kei; Tamai, Mami; Kamachi, Makoto; Satoh, Katsuya; Origuchi, Tomoki; Kawakami, Atsushi; Furuichi, Itaru; Kawabe, Yojiro; Eguchi, Katsumi

doi:10.1007/s10616-009-9229-5

Cited by 2 publications

(2 citation statements)

References 27 publications

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“… 33 Synoviocytes are known to express gp130 but not IL-6R, and can therefore only respond to IL-6 in the presence of sIL-6R. 31 We previously observed that chondrocytes express gp130, IL-6R, and sIL-6R. 34 Here, we further show that HIF-2α upregulates IL-6R in chondrocytes but not FLS, suggesting that FLS-derived IL-6 may critically mediate the functions of chondrocytes.…”

Section: Discussionmentioning

confidence: 49%

“…29 In addition, an anti-IL-6 antibody was shown to inhibit RA in an experimental mouse model, and the humanized anti-IL-6 receptor antibody, tocilizumab, is used as an immunosuppressive drug in RA patients. 30 TNF-α can bind to two specific receptors, TNFR1 and TNFR2, which are both expressed in RA synovium 31 and OA cartilage. 32 Here, we show that HIF-2α upregulates TNFR2 (encoded by Tnfrsf1b ) in FLS but not chondrocytes, suggesting that chondrocyte-derived TNF-α may critically mediate the functions of FLS.…”

Section: Discussionmentioning

confidence: 99%

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Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis

et al. 2015

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Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently demonstrated that hypoxia-inducible factor (HIF)-2α causes RA and OA by regulating the expression of catabolic factors in fibroblast-like synoviocytes (FLS) or chondrocytes. To address the reciprocal influences of HIF-2α on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2α-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-α treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2α-overexpressing FLS exhibited upregulation of Mmp3 and Mmp13, which is similar to the effects induced by interleukin (IL)-6 treatment of chondrocytes. We confirmed these differential HIF-2α-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-α-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-α neutralization blocked the alterations in gene expression associated with co-culture of FLS with chondrocytes. Our results further suggested that the observed changes might reflect the HIF-2α-induced upregulation of specific receptors for TNF-α (in FLS) and IL-6 (in chondrocytes). This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2α, and may suggest potential new anti-arthritis therapies.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis

et al. 2015

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Differential pro-inflammatory responses of TNF-α receptors (TNFR1 and TNFR2) on LOX-1 signalling

Arjuman

Chandra

2014

Mol Biol Rep

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TNF-α potently induces LOX-1 expression in THP-1 macrophages at concentrations between 1.25-50 ng/mL. The interplay between the two TNF receptors (TNFR1 and TNFR2) was apparent in the expression pattern of LOX-1 in response to TNF-α. Interestingly, R1 signal abrogation depleted both TNFR2 as well as LOX-1 transcript expression, suggesting that TNFR1 holds priority in the relative signaling mechanism between TNFR1 and TNFR2. TNF-α was also found to abrogate the oxidized-LDL (ox-LDL) mediated increase in intracellular pool of NO, a known downstream intermediate of LOX-1 pro-inflammatory signaling cascade. At the level of ox-LDL clearance, TNF-α inhibited the uptake (scavenging) of ox-LDL via LOX-1. Our study demonstrates the ability of TNF-α to enhance the signaling propensity of LOX-1 by increasing its expression and inhibiting its scavenging property.

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Different expression levels of TNF receptors on the rheumatoid synovial macrophages derived from surgery and a synovectomy as detected by a new flow cytometric analysis

Cited by 2 publications

References 27 publications

Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis

Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis

Differential pro-inflammatory responses of TNF-α receptors (TNFR1 and TNFR2) on LOX-1 signalling

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