Persistent Induction of the Chemokine Receptor CXCR4 by TGF-β1 on Synovial T Cells Contributes to Their Accumulation Within the Rheumatoid Synovium

Buckley, CD; Amft, Nicole; Bradfield, Paul F.; Pilling, Darrell; Ross, Emma J.; Arenzana-Seisdedos, F; Amara, Ali; Curnow, S. John; Lord, Janet M.; Scheel‐Toellner, Dagmar; Salmon, Mike

doi:10.4049/jimmunol.165.6.3423

Cited by 315 publications

(283 citation statements)

References 39 publications

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“…For example, TGF-β1 has been reported to induce the expression of CXCR4 on dendritic cells [17,18] . Similar results were also observed in eosinophils, CD4 + T cells , macrophages derived from monocytes [19][20][21] , and so on. Moreover, Javelaud et al found that TGF-β1 upregulated CXCR4 mRNA expression in melanoma cells [22] .…”

Section: Introductionsupporting

confidence: 70%

Transforming growth factor-β1 upregulates the expression of CXC chemokine receptor 4 (CXCR4) in human breast cancer MCF-7 cells

Zhao

Huang

et al. 2010

Acta Pharmacol Sin

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Aim: To investigate whether rhTGF-β1 or a recombinant vector encoding a fusion protein comprising an extracellular domain of TGF-β receptor II and an IgG Fc fragment) affects the regulation of CXC chemokine receptor 4 (CXCR4) expression in MCF-7 human breast cancer cells. Methods: MCF-7 breast cancer cells were treated with rhTGF-β1 or transfected with a recombinant vector, pIRES2-EGFP-TβRII-Fc. Expression of CXCR4 in these cells was then analyzed at the mRNA and protein levels by quantitative RT-PCR and flow cytometry assay, respectively. A transwell assay was used to measure the chemotactic response of these cells to SDF-1α. Results: CXCR4 mRNA and protein expression were upregulated in TGF-β1-treated MCF-7 cells. These cells also demonstrated an enhanced chemotactic response to SDF-1α. In MCF-7 cells transiently transfected with pIRES2-EGFP-TβRII-Fc, a fusion protein named TβRII-Fc (approximately 41 kDa) was produced and secreted. In these transfected cells, there was a reduction in CXCR4 expression and in the SDF-1α-mediated chemotactic response. Conclusion: TGF-β1 upregulated CXCR4 expression in MCF-7 cells, which subsequently enhanced the SDF-1α-induced chemotactic response. The results suggest a link between TGF-β1 and CXCR4 expression in MCF-7 human breast cancer cells, which may be one of the mechanisms of TGF-β1-mediated enhancement of metastatic potential in breast cancer cells.

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Section: Introductionsupporting

confidence: 70%

Transforming growth factor-β1 upregulates the expression of CXC chemokine receptor 4 (CXCR4) in human breast cancer MCF-7 cells

Zhao

Huang

et al. 2010

Acta Pharmacol Sin

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“…CXCR4 is rapidly up-regulated after both PHA stimulation and IL-2 priming. In the RA synovium, T cells are induced to express CXCR4, and transforming growth factor ␤ is demonstrated to be responsible for the expression (Buckley et al, 2000). These CXCR4-positive synovial T cells show better adherence to fibronectin in response to SDF-1 than PBL.…”

Section: Terada Et Almentioning

confidence: 99%

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

Terada

Yamamoto

Hakoda

et al. 2003

Laboratory Investigation

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SUMMARY:Although stromal cell-derived factor-1 (SDF-1) plays an important role in hematopoiesis in the fetal liver, the role after birth remains to be clarified. We investigated the role of SDF-1 and its receptor, CXCR4, in 75 patients; this included controls and patients with viral hepatitis, liver cirrhosis, primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Interestingly, SDF-1 appeared up-regulated in biliary epithelial cells (BEC) of inflammatory liver disease. Furthermore, in inflammatory liver diseases, SDF-1 was expressed by BEC of interlobular and septal bile ducts and by proliferated bile ductules. The message expression of SDF-1 in BEC was confirmed at a single-cell level by RT-PCR and laser capture microdissection. The plasma levels of SDF-1 were significantly higher in patients with liver diseases than in normal controls. Flow cytometric analysis of the surface expression of CXCR4 showed that most liver-infiltrating lymphocytes express CXCR4 and the intensity was up-regulated more significantly in liver-infiltrating lymphocytes than in peripheral blood lymphocytes. These results suggest that increased SDF-1 production by BEC may play an important role in the recruitment of CXCR4-positive inflammatory cells into the diseased livers. These data are significant because modulation of the SDF-1/CXCR4 interaction has therapeutic implications for inflammatory liver diseases. (Lab Invest 2003, 83:665-672).

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“…Only recently it was recognized that stromal cell-derived factor-1 (SDF-1), the only known ligand of CXCR4, also plays a role in inflammatory diseases like rheumatoid arthritis [4]. More than 90% of the infiltrating T cells in the inflamed synovial membrane and synovial fluid express CXCR4 [5].…”

Section: Introductionmentioning

confidence: 99%

Post‐translational and cell type‐specific regulation of CXCR4 expression by cytokines

Brühl¹,

Cohen²,

Linder³

et al. 2003

Eur J Immunol

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We have investigated the regulation and function of the chemokine receptor CXCR4 on neutrophils. CXCR4 is hardly detectable on neutrophils in the peripheral blood. However, overnight culture strongly up-regulates CXCR4 expression on the cell surface. The functional activity of CXCR4 on cultured neutrophils was confirmed by stromal cell-derived factor (SDF)-induced migration and up-regulation of the integrins CD11b and CD11c. CXCR4 surface expression on neutrophils but not on lymphocytes and monocytes is rapidly downregulated after stimulation with TNF- § and IFN-+ , resulting in significantly decreased SDFinduced functional responses of neutrophils. In contrast to surface expression, CXCR4 mRNA expression was several-fold increased in cytokine-stimulated neutrophils, suggesting a post-translational regulation. By confocal microscopy we demonstrate that CXCR4 is internalized after stimulation with TNF- § and IFN-+ . b he down-modulation of CXCR4 surface expression in response to TNF- § and IFN-+ was fully reversible after cytokine removal. Further, CXCR4 down-modulation could be completely blocked by hypertonic sucrose and significantly reduced by chlorpromazine indicating the involvement of clathrin-coated pits. Internalization of CXCR4 by cytokines in a cell type-specific manner is a novel and functionally important mechanism of chemokine receptor regulation.

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Persistent Induction of the Chemokine Receptor CXCR4 by TGF-β1 on Synovial T Cells Contributes to Their Accumulation Within the Rheumatoid Synovium

Cited by 315 publications

References 39 publications

Transforming growth factor-β1 upregulates the expression of CXC chemokine receptor 4 (CXCR4) in human breast cancer MCF-7 cells

Transforming growth factor-β1 upregulates the expression of CXC chemokine receptor 4 (CXCR4) in human breast cancer MCF-7 cells

Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

Post‐translational and cell type‐specific regulation of CXCR4 expression by cytokines

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