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Tumor Necrosis Factor Receptor I (tumor + necrosis_factor_receptor_i)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Antiinflammatory effects of tumor necrosis factor on hematopoietic cells in a murine model of erosive arthritis

ARTHRITIS & RHEUMATISM, Issue 6 2010
Stephan Blüml
Objective To investigate the mechanisms leading to the influx of inflammatory hematopoietic cells into the synovial membrane and the role of tumor necrosis factor receptor I (TNFRI) and TNFRII in this process in an animal model of rheumatoid arthritis (RA). Methods We performed bone marrow transplantations in human TNF,transgenic mice using hematopoietic cells from wild-type, TNFRI,/,, TNFRII,/,, and TNFRI/II,/, mice as donors and assessed the severity of arthritis histologically. Generation of osteoclasts from the different genotypes was analyzed in vitro and in vivo. Apoptosis was analyzed using annexin V staining as well as TUNEL assays. Results Despite lacking responsiveness to TNF in their hematopoietic compartment, mice not only developed full-blown erosive arthritis but even showed increased joint destruction when compared with mice with a TNF-responsive hematopoietic compartment. We demonstrated different roles of the 2 different TNFRs in the regulation of these processes. The absence of TNFRI on hematopoietic cells did not affect joint inflammation but markedly attenuated erosive bone destruction via reduced synovial accumulation of osteoclast precursors. In contrast, the absence of TNFRII on hematopoietic cells increased joint inflammation as well as erosive bone destruction via the regulation of osteoclast precursor apoptosis. Conclusion Our findings indicate that selective blockade of TNFRI, leaving the antiinflammatory effects of TNFRII unaltered instead of unselectively blocking TNF, might be advantageous in patients with RA. [source]

Unmasking of a protective tumor necrosis factor receptor I,mediated signal in the collagen-induced arthritis model

ARTHRITIS & RHEUMATISM, Issue 2 2009
Cheryll Williams-Skipp
Objective To examine the relative importance of tumor necrosis factor receptor I (TNFRI) signaling in the hematopoietic tissue compartment in the progression of collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). Methods DBA/1 mice were administered a lethal radiation dose and were then rescued with bone marrow derived from either DBA/1 or TNFRI,/, mice. CIA was then induced, and disease progression was characterized. Results Surprisingly, mice with CIA that received TNFRI,/, donor marrow developed increased disease severity as compared with control mice with CIA. This could not be attributed to an increased primary response to collagen or to the contribution of a non-DBA genetic background. In mice that received TNFRI,/, bone marrow, histologic markers of advanced disease were evident shortly after initiation of the immune response to collagen and long before clinical evidence of disease. Serum TNF, was undetectable, whereas serum interleukin-12 p40 levels were increased, at the end point of the study in mice that received TNFRI,/, bone marrow. Conclusion These data raise the intriguing possibility of the existence of an antiinflammatory, TNFRI-mediated circuit in the hematopoietic compartment. This circuit bears a resemblance to the switch in TNF, function that has been observed during the resolution of bacterial infections. These data suggest that TNFRI-mediated signals in the radioresistant tissues contribute to disease progression, whereas TNFRI-mediated signals in the radiosensitive tissues can contribute to protection from disease. We thus put forward the hypothesis that the degree of response to TNF, blockade in RA is dependent in part on the relative genetic strengths of these 2 pathways. [source]

Association between serum levels of soluble tumor necrosis factor receptors/CA 125 and disease progression in patients with epithelial ovarian malignancy,,

CANCER, Issue 1 2004
A Gynecologic Oncology Group study
Abstract BACKGROUND A prospective study was undertaken within the Gynecologic Oncology Group to determine whether serum levels of soluble tumor necrosis factor receptors I (sTNFR-I) and II (sTNFR-II), alone or in combination with CA 125, were associated with clinicopathologic characteristics or outcome in patients with epithelial ovarian malignancies. METHODS Quantitative immunoassays were performed on valid pretreatment serum specimens obtained from patients with epithelial ovarian malignancies to assess levels of sTNFR-I, sTNFR-II, and CA 125. The authors then analyzed the results of these immunoassays for potential correlations with clinicopathologic characteristics and outcome. RESULTS The median age of the 139 women evaluated was 59 years. Seventy-eight percent had Stage III or IV disease, and 58% had serous carcinomas. sTNFR-II was associated with age (P = 0.013), and CA 125 was associated with histologic subtype (P = 0.0009). In addition, sTNFR-I (P = 0.037) and CA 125 (P < 0.0001) were associated with extent of disease. After adjusting for patient age, histologic subtype, and extent of disease, all three biomarkers were predictive of progression-free survival, but not overall survival, when the combination was included in the model. The authors observed a 51% reduction (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.24,0.99), a 2.9-fold increase (HR, 2.87; 95% CI, 1.15,7.20), and a 22% increase (HR, 1.22; 95% CI, 0.99,1.51) in the risk of progression for each unit increase in the log-transformed levels of sTNFR-I, sTNFR-II, and CA 125, respectively. CONCLUSIONS The observations made in the current study,that among patients with low or high CA 125 levels, those with high sTNFR-I levels and low sTNFR-II levels had the lowest risk, that patients with low-low or high-high sTNFR-I and sTNFR-II levels, respectively, had an intermediate risk, and that patients with low sTNFR-I levels and high sTNFR-II levels had the highest risk of progression,suggested the potential value of simultaneous assessment of all three biomarkers in patients with epithelial ovarian malignancies. Cancer 2004. © 2004 American Cancer Society. [source]