scholarly journals Essential Role of Nuclear Factor (NF)-κB–Inducing Kinase and Inhibitor of κb (Iκb) Kinase α in Nf-κb Activation through Lymphotoxin β Receptor, but Not through Tumor Necrosis Factor Receptor I

2001 ◽  
Vol 193 (5) ◽  
pp. 631-636 ◽  
Author(s):  
Akemi Matsushima ◽  
Tsuneyasu Kaisho ◽  
Paul D. Rennert ◽  
Hiroyasu Nakano ◽  
Kyoko Kurosawa ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Essential Role ◽  
Nuclear Factor ◽  
Wild Type ◽  
Embryonic Fibroblasts ◽  
Iκb Kinase ◽  
Β Receptor ◽  
Deficient Mice ◽  
Necrosis Factor

Both nuclear factor (NF)-κB–inducing kinase (NIK) and inhibitor of κB (IκB) kinase (IKK) have been implicated as essential components for NF-κB activation in response to many external stimuli. However, the exact roles of NIK and IKKα in cytokine signaling still remain controversial. With the use of in vivo mouse models, rather than with enforced gene-expression systems, we have investigated the role of NIK and IKKα in signaling through the type I tumor necrosis factor (TNF) receptor (TNFR-I) and the lymphotoxin β receptor (LTβR), a receptor essential for lymphoid organogenesis. TNF stimulation induced similar levels of phosphorylation and degradation of IκBα in embryonic fibroblasts from either wild-type or NIK-mutant mice. In contrast, LTβR stimulation induced NF-κB activation in wild-type mice, but the response was impaired in embryonic fibroblasts from NIK-mutant and IKKα-deficient mice. Consistent with the essential role of IKKα in LTβR signaling, we found that development of Peyer's patches was defective in IKKα-deficient mice. These results demonstrate that both NIK and IKKα are essential for the induction of NF-κB through LTβR, whereas the NIK–IKKα pathway is dispensable in TNFR-I signaling.

scholarly journals Distinct Roles of Lymphotoxin α and the Type I Tumor Necrosis Factor (TNF) Receptor in the Establishment of Follicular Dendritic Cells from Non–Bone Marrow–derived Cells

1997 ◽  
Vol 186 (12) ◽  
pp. 1997-2004 ◽  
Author(s):  
Mitsuru Matsumoto ◽  
Yang-Xin Fu ◽  
Hector Molina ◽  
Guangming Huang ◽  
Jinho Kim ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Tumor Necrosis ◽  
Type I ◽  
Follicular Dendritic Cells ◽  
Wild Type ◽  
Lymphotoxin Α ◽  
Deficient Mice ◽  
Necrosis Factor

In mice deficient in either lymphotoxin α (LT-α) or type I tumor necrosis factor receptor (TNFR-I), organized clusters of follicular dendritic cells (FDC) and germinal centers (GC) are absent from the spleen. We investigated the role of LT-α and TNFR-I in the establishment of spleen FDC and GC structure by using reciprocal bone marrow (BM) transfer. When LT-α–deficient mice were reconstituted with wild-type BM, FDC organization and the ability to form GC were restored, indicating that the LT-α–expressing cells required to establish organized FDC are derived from BM. The role of LT-α in establishing organized FDC structure was further investigated by the transfer of complement receptor 1 and 2 (CR1/2)–deficient BM cells into LT-α–deficient mice. Organized FDC were identified with both the FDC-M1 and anti-CR1 monoclonal antibodies in these BM-chimeric mice, indicating that these cells were derived from the LT-α–deficient recipient. Thus, expression of LT-α in the BM-derived cells, but not in the non–BM-derived cells, is required for the maturation of FDC from non-BM precursor cells. In contrast, when TNFR-I–deficient mice were reconstituted with wild-type BM, they showed no detectable FDC clusters or GC formation. This indicates that TNFR-I expression on non–BM-derived cellular components is necessary for the establishment of these lymphoid structures. TNFR-I–deficient BM was able to restore FDC organization and GC formation in LT-α–deficient mice, indicating that formation of these structures does not require TNFR-I expression on BM-derived cells. The data in this study demonstrate that FDC organization and GC formation are controlled by both LT-α–expressing BM-derived cells and by TNFR-I-expressing non–BM-derived cells.

The Role of Nuclear Factor-kappaB and Melanogenesis in Tumor Necrosis Factor-Alpha-Induced Apoptosis of Normal Human Melanocytes

2002 ◽  
Vol 15 (5) ◽  
pp. 321-329 ◽  
Author(s):  
Jing Shang ◽  
Jürgen Eberle ◽  
Christoph C. Geilen ◽  
Amir M. Hossini ◽  
Lothar F. Fecker ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Necrosis Factor Alpha ◽  
Human Melanocytes ◽  
Normal Human ◽  
Factor Alpha ◽  
Induced Apoptosis ◽  
Necrosis Factor

scholarly journals Crucial Role of Tumor Necrosis Factor Receptor 1 Expression on Nonhematopoietic Cells for B Cell Localization within the Splenic White Pulp

1998 ◽  
Vol 187 (4) ◽  
pp. 469-477 ◽  
Author(s):  
Maria Tkachuk ◽  
Stephan Bolliger ◽  
Bernhard Ryffel ◽  
Gerd Pluschke ◽  
Theresa A. Banks ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis ◽  
Plasma Cells ◽  
Tumor Necrosis Factor Receptor ◽  
White Pulp ◽  
Splenic White Pulp ◽  
Initial Activation ◽  
Deficient Mice ◽  
Necrosis Factor

During immune responses the initial activation of B cells takes place in T cell zones of periarteriolar lymphoid sheaths (PALS) of the splenic white pulp. After initial activation, B cells migrate into the primary follicles and, in association with follicular dendritic cells (FDCs), undergo clonal expansion and differentiation giving rise to germinal centers (GCs). Peanut agglutinin binding (PNA+) cells of the GC differentiate further into memory or plasma cells. Here we report that in tumor necrosis factor receptor 1–deficient mice (TNFR1−/−), the location of B cells was altered and that plasma cells were abnormally distributed in the splenic PALS. In contrast to lymphotoxin α–deficient mice (LTα−/−), bone marrow or fetal liver transplantation did not correct the abnormal organization of the spleen, location of B cells, the lack of an FDC network, nor the antibody response in TNFR1−/− mice. These results argue for a crucial role of TNFR1 expression on nonhematopoietic cells for the maintenance of the splenic architecture and proper B cell location. In addition, the lack in development of an FDC network after adoptive transfer suggests that either FDCs are not of bone marrow origin or that they depend on signals from nonhematopoietic cells for maturation.

scholarly journals Upregulation of CASP9 through NF-κB and Its Target MiR-1276 Contributed to TNFα-Promoted Apoptosis of Cancer Cells Induced by Doxorubicin

2020 ◽  
Vol 21 (7) ◽  
pp. 2290
Author(s):  
Fei Zhou ◽  
Yun Li ◽  
Yisheng Huang ◽  
Jian Wu ◽  
Qinhan Wu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Hepg2 Cells ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Apoptotic Pathway ◽  
Factor Α ◽  
Necrosis Factor

Under some conditions, nuclear factor-κB (NF-κB) has a pro-apoptotic role, but the mechanisms underlying this function remain unclear. This study demonstrated that NF-κB directly binds to CASP9 and miR1276 in tumor necrosis factor α (TNFα)-treated HeLa and HepG2 cells. NF-κB upregulated CASP9 expression, whereas downregulated miR1276 expression in the TNFα-treated cells. The miR1276 repressed CASP9 expression in both cells. As a result, a typical NF-κB-mediated coherent feed-forward loop was formed in the TNFα-treated cells. It was proposed that the NF-κB-mediated loop may contribute to cell apoptosis under certain conditions. This opinion was supported by the following evidence: TNFα promoted the apoptosis of HeLa and HepG2 cells induced by doxorubicin (DOX). CASP9 was significantly upregulated and activated by TNFα in the DOX-induced cells. Moreover, a known inhibitor of CASP9 activation significantly repressed the TNFα promotion of apoptosis induced by DOX. These findings indicate that CASP9 is a new mediator of the NF-κB pro-apoptotic pathway, at least in such conditions. This study therefore provides new insights into the pro-apoptotic role of NF-κB. The results also shed new light on the molecular mechanism underlying TNFα-promotion of cancer cells apoptosis induced by some anticancer drugs such as DOX.

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