Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein

Iwata, Mineo; Graf, Lynn; Awaya, Norihiro; Torok‐Storb, Beverly

doi:10.1182/blood-2002-01-0062

Cited by 44 publications

(30 citation statements)

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“…IL-7 has been shown to stimulate cytokine secretion from IL-7R-expressing BM stromal cells [22]. Another downstream cytokine in IL-7 over-expressing environment could be RANKL, the key osteoclastogenic factor that binds to its RANK receptor on OCL precursors [15] and is able to induce CD45R + cell proliferation in combination with IL-7 [23]. RANKL, shown to increase with IL-7 stimulation of T lymphocytes [15], mediates bone resorption together with tumor necrosis factor-α in IL-7 treated mice [18].…”

Section: Discussionmentioning

confidence: 99%

Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter

et al. 2008

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“…Formaldehyde RNA agarose gels, capillary blotting, and hybridization were conducted as previously described. 26,27 The blot was exposed to a phosphor screen that was quantitatively scanned by a Typhoon scanner (Molecular Dynamics, Santa Cruz, CA), and analysis was done using ImageQuant software, also from Molecular Dynamics. …”

mentioning

confidence: 99%

“…Forty microliters of the extracts were applied to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using a precast 10% polyacrylamide gel (Invitrogen, Carlsbad, CA) followed by immunoblot with PY-20 antiphosphotyrosine antibody (Transduction Laboratories, Lexington, KY) as described elsewhere. 27 Bench Mark protein ladder (Gibco, Rockville, MD) was used to calculate molecular weight of the phosphorylated proteins. …”

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confidence: 99%

Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells

Iwata

Awaya

Graf

et al. 2004

Blood

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The hematopoietic microenvironment, approximated in vitro by long-term marrow cultures (LTCs), consists of both nonhematopoietic-derived stromal elements and hematopoietic-derived monocyte/macrophages. To better understand the consequences of monocyte-stroma interactions, we compared gene expression profiles of CD14 ؉ peripheral blood monocytes and HS-27a stromal cells cultured alone and together in cocultures. Results from 7 separate experiments revealed 22 genes were significantly up-or downregulated in the cocultures, with osteopontin (OPN) up-regulated more than 15-fold. The microarray OPN data were confirmed by Northern blot, real-time polymerase chain reaction (PCR), and by detection of OPN protein. High levels of OPN gene expression were also detected in 2-to 3-week-old primary LTCs. Using Transwells we determined that stromal cells were secreting a factor that upregulated OPN gene expression in CD14 ؉ cells. When CD34 ؉ cells were cultured in the presence of purified OPN, tyrosine phosphorylation of a 34-kDa molecule was increased 2-to 3-fold, an effect that was diminished in the presence of an OPN neutralizing monoclonal antibody. In addition, Notch1 gene expression was decreased 5-fold in OPN-treated CD34 ؉ cells. We conclude that interactions between stroma and monocytes can result in activities that limit the role of Notch signaling in hematopoietic regulation. IntroductionThe hematopoietic microenvironment (ME), defined largely by function, is a complex mixture of cells and factors critical for the regulation of hematopoiesis. The ME is assayed in vitro using primary long-term marrow cultures (LTCs) that consist of nonhematopoietic-derived stromal components as well as hematopoietic components, including monocytes and macrophages. A critical in vivo role for the macrophage in the marrow ME has long been inferred from histologic studies, best exemplified by the nurse cell of the erythropoietic island. In primary LTCs, up to 40% of all cells can be macrophages even after 12 weeks of culture. 1 These cells are known to secrete many cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), and tumor necrosis factor (TNF), all of which have direct effects on hematopoietic cells. Monocytes/macrophages are also capable of stimulating stromal cells to produce cytokines. [2][3][4][5] Because macrophages also produce transforming growth factor-␤ (TGF␤) and platelet-derived growth factor (PDGF), both of which can influence the mitotic rate of fibroblasts, the macrophage may also be capable of regulating stromal cell growth. [6][7][8][9][10] Gaining a more precise understanding of monocyte-stroma interactions within the ME is complicated by the heterogeneous nature of the stromal compartment. In an effort to functionally dissect the ME, several groups have established cloned stromal cell lines that identify individual ME components. [11][12][13][14][15] We previously reported on immortalized human marrow stromal ce...

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“…18 On the other hand, it is necessary to detect the expression level of IL-7 receptor and its downstream signaling because the presence of IL-7 receptor has been shown in human bone marrow stromal cells. 36 The above mysteries should be further investigated in future work. In summary, our data indicate that IL-7 has no effect on the proliferation of human PDLSCs, but it markedly inhibits the osteogenic differentiation of human PDLSCs, decreases ALP activity, and downregulates the expression of Runx-2, SP7, and OCN genes and proteins possibly through suppressing the phosphorylation of JNK, ERK1/2, and p38 proteins.…”

Section: Il-7 Inhibits Osteogenic Differentiation Of Pdlscsmentioning

confidence: 99%

IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway

Cao

Fan²,

Yonghe³

et al. 2016

Organogenesis

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ABSTRACT. Periodontal ligament stem cells (PDLSCs) are tissue-specific mesenchymal stem cells (MSCs), having an important role in regenerative therapy for teeth loss. Interleukin-7 (IL-7) is a key cytokine produced by stromal cells including MSCs, and exhibits specific roles for B and T cell development and osteoblasts differentiation of multiple myeloma. However, the effect of IL-7 on osteogenic differentiation of PDLSCs remains unclear. Therefore, in the present study we determined whether IL-7 affects the proliferation and osteogenic differentiation of PDLSCs in vitro and explored the associated signaling pathways for IL-7-mediated cell differentiation. The results demonstrated that the isolated human PDLSCs possessed MSCs features, highly expressing CD90, CD44, CD105, CD29 and CD73, and almost did not expressed CD34, CD45, CD11b, CD14 and CD117. IL-7 could not significantly affect the proliferation of PDLSCs, but it decreased their osteogenic differentiation and inhibited alkaline phosphatase (ALP) activity. The results of quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) and Western blotting exhibited that the expression levels of Runx-2, SP7 and osteocalcin (OCN) were significantly reduced by IL-7. Further studies indicated that IL-7 did not significantly change JNK, ERK1/2 and p38 protein production, but markedly suppressed their phosphorylation levels. These data suggest that IL-7 inhibits the osteogenic differentiation of PDLSCs probably via inactivation of mitogen-activated protein kinase (MAPK) signaling pathway.

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Functional interleukin-7 receptors (IL-7Rs) are expressed by marrow stromal cells: binding of IL-7 increases levels of IL-6 mRNA and secreted protein

Cited by 44 publications

References 33 publications

Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter

Increased bone resorption and osteopenia are a part of the lymphoproliferative phenotype of mice with systemic over-expression of interleukin-7 gene driven by MHC class II promoter

Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells

IL-7 suppresses osteogenic differentiation of periodontal ligament stem cells through inactivation of mitogen-activated protein kinase pathway

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