Lipopolysaccharide from<i>Salmonella enterica</i>Activates NF-κB through both Classical and Alternative Pathways in Primary B Lymphocytes

Souvannavong, Vongthip; Saidji, Nabila; Chaby, Richard

doi:10.1128/iai.00545-07

Cited by 22 publications

(20 citation statements)

References 52 publications

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“…Our findings, demonstrating that LPS can activate both classical and alternative NF-kB pathways both in primary lung epithelial cells and in lung tissue, are supported by previous work demonstrating the activation of both classical and alternative NF-kB pathways by LPS in B lymphocytes (33). Similarly, TNF-a, an agonist of the classical NF-kB pathway, has been shown to activate the alternative NF-kB pathway in murine embryonic fibroblasts (34,35).…”

Section: Discussionsupporting

confidence: 75%

Cooperation between Classical and Alternative NF-κB Pathways Regulates Proinflammatory Responses in Epithelial Cells

Tully

Nolin²,

Guala³

et al. 2012

Am J Respir Cell Mol Biol

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The transcription factor NF-kB has been causally linked to inflammatory lung diseases. Recent studies have unraveled the complexity of NF-kB activation by identifying two parallel activation pathways: the classical NF-kB pathway, which is controlled by IkB kinase complex-b (IKKb) and RelA/p50, and the alternative pathway, which is controlled by IKKa and RelB/p52. The alternative pathway regulates adaptive immune responses and lymphoid development, yet its role in the regulation of innate immune responses remains largely unknown. In this study, we determined the relevance of the alternative NF-kB pathway in proinflammatory responses in lung epithelial cells. The exposure of C10 murine alveolar lung epithelial cells to diverse stimuli, or primary murine tracheal epithelial cells to LPS, resulted in the activation of both NF-kB pathways, based on the nuclear translocation of RelA, p50, RelB, and p52. Increases in the nuclear content of RelA occurred rapidly, but transiently, whereas increases in nuclear RelB content were protracted. The small interfering (si) RNAmediated knockdown of IKKa, RelA, or RelB resulted in decreases of multiple LPS-induced proinflammatory cytokines. Surprisingly, the siRNA ablation of IKKa or RelB led to marked increases in the production of IL-6 in response to LPS. The simultaneous expression of constitutively active (CA)-IKKa and CA-IKKb caused synergistic increases in proinflammatory mediators. Lastly, the disruption of the IKK signalsome inhibited the activation of both NF-kB pathways. These results demonstrate that the coordinated activation of both NF-kB pathways regulates the magnitude and nature of proinflammatory responses in lung epithelial cells.Keywords: lung; IkB kinase-b; IkB kinase-a; RelA; RelB NF-kB is a transcription factor that plays a cardinal role in multiple cellular processes, including survival, proliferation, and inflammation. In unstimulated cells, NF-kB dimers RelA and p50 are sequestered in the cytosol by the inhibitor of kB (IkBa). The IkB kinase complex (IKK) consists of two catalytic subunits, IKKb and IKKa, and the regulatory protein, IKKg (also known as NF-kB essential modulator). Upon ligation by a variety of stimuli such as TNF-a or Toll-like receptor agonists, IKKb is phosphorylated and in turn phosphorylates IkBa, leading to its subsequent ubiquitination and degradation by the 26S proteasome (1, 2). The processing of IkBa promotes the nuclear translocation of RelA/p50, leading to the transcriptional activation of NF-kB-dependent genes. NF-kB activates the transcription of many proinflammatory cytokine and chemokine genes that initiate and propagate innate immune responses (1, 2).The airway epithelium, classically regarded as the first line of defense against inhaled agents, toxic factors, and physical trauma, is now recognized as a key component of the innate immune system, and plays an active role in the orchestration of acute inflammatory and adaptive immune responses (3, 4). Upon stimulation, epithelial cells secrete proinflammatory mediators such as...

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Section: Discussionsupporting

confidence: 75%

Cooperation between Classical and Alternative NF-κB Pathways Regulates Proinflammatory Responses in Epithelial Cells

Tully

Nolin²,

Guala³

et al. 2012

Am J Respir Cell Mol Biol

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“…The disorder of commensal flora is the trigger to priming the intestinal inflammation [25]. LPS is the main virulence of Gram negative bacterial and main cause to perpetuate inflammatory response [9]. TLR4 is an important pattern recognition receptor to recognize antigen and bridge innate immunity and adaptive immunity [8].…”

Section: Discussionmentioning

confidence: 99%

“…LPS is the predominant product of Gram negative bacteria and is the main ligand of toll like receptor 4 (TLR4). It is known that the intestinal mucosa immunity, in response to LPS, produces functional TLR4 and which in turn releases cytokine products to maintain the immune balance in the intestinal mucosa of the healthy animals [9]. Recent reports have demonstrated that the LPS/TLR4/NF-κB pathway plays a crucial role in the initiation and development of IBD [10,11].…”

Section: Introductionmentioning

confidence: 99%

Immunomodulation of Rheum tanguticum polysaccharide (RTP) on the immunosuppressive effects of dexamethasone (DEX) on the treatment of colitis in rats induced by 2,4,6-trinitrobenzene sulfonic acid

Liu

Yuan

Yin

et al. 2009

International Immunopharmacology

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“…To determine if PU.1 interaction with the Nfkb1 promoter was reduced in PUB B cells, chromatin was prepared from freshly isolated and LPS-stimulated B cells and immunoprecipitated with anti-PU.1 or control Abs. WT and PUB B cells were LPS stimulated for 16 h, as this time point provided increased p50 expression upon LPS exposure (45). Relative amounts of immunoprecipitated DNA were determined by qPCR from the Nfkb1 promoter region, the positive-control Mef2c gene enhancer (13), and the negative-control Hprt gene.…”

Section: Pubmentioning

confidence: 99%

Nfkb1 Activation by the E26 Transformation-Specific Transcription Factors PU.1 and Spi-B Promotes Toll-Like Receptor-Mediated Splenic B Cell Proliferation

Abbas

Solomon

et al. 2015

Molecular and Cellular Biology

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Murine B cells express and respond to TLR1, TLR2, TLR4, TLR6, TLR7/8, and TLR9 ligands (6-8), resulting in NF-B activation through MyD88 or TRIF (TIR domain-containing adapter inducing beta interferon)-dependent pathways (9). NF-B activates genes involved in cytokine synthesis, antibody secretion, and cell proliferation (10). The NF-B family includes p105, which is processed into p50 (encoded by Nfkb1), p100 that is processed into p52 (encoded by Nfkb2), RelA (p65), Rel (c-Rel), and RelB, which all interact with DNA as hetero-or homodimers (11). Full TLR signaling in B cells may require major histocompatibility complex class II (MHC-II) interaction with Bruton's tyrosine kinase (Btk) and CD40 (12). However, many aspects of gene regulation involving TLR expression and signal transduction in B cells remain unclear.PU.1 and Spi-B are E26 transformation-specific (ETS) family transcription factors encoded by Sfpi1 and Spib, respectively, and are important in B cell development and function (13). PU.1 is expressed in most hematopoietic cell types, directly regulating many genes involved in cellular communication (14). Spi-B is expressed in B cells, in plasmacytoid dendritic cells, and, at lower levels, in T cells (15). PU.1 and Spi-B share 67% amino acid homology in their DNA binding domain and can bind an identical consensus sequence containing the core motif 5=-GGAA-3= (16-18). Both transcription factors are expressed in B cells, regulate common target genes, and are functionally redundant (19,20 In this study, it was determined whether PU.1 and Spi-B regulate innate immune responses in B cells. Impairment in TLR-mediated proliferation in PUB B cells was observed. Gene and protein expression analysis, luciferase reporter assays, and chromatin im- Citation Li SKH, Abbas AK, Solomon LA, Groux GMN, DeKoter RP. 2015. Nfkb1 activation by the E26 transformation-specific transcription factors PU.1 and Spi-B promotes Toll-like receptor-mediated splenic B cell proliferation.

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Lipopolysaccharide fromSalmonella entericaActivates NF-κB through both Classical and Alternative Pathways in Primary B Lymphocytes

Cited by 22 publications

References 52 publications

Cooperation between Classical and Alternative NF-κB Pathways Regulates Proinflammatory Responses in Epithelial Cells

Cooperation between Classical and Alternative NF-κB Pathways Regulates Proinflammatory Responses in Epithelial Cells

Immunomodulation of Rheum tanguticum polysaccharide (RTP) on the immunosuppressive effects of dexamethasone (DEX) on the treatment of colitis in rats induced by 2,4,6-trinitrobenzene sulfonic acid

Nfkb1 Activation by the E26 Transformation-Specific Transcription Factors PU.1 and Spi-B Promotes Toll-Like Receptor-Mediated Splenic B Cell Proliferation

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