NF-κB Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions

Caamaño, Jorge H.; Hunter, Christopher A.

doi:10.1128/cmr.15.3.414-429.2002

Cited by 462 publications

(376 citation statements)

References 230 publications

Supporting

Mentioning

349

Contrasting

Unclassified

Order By: Relevance

“…However, NF-B family members can also influence multiple DC functions, including expression of costimulatory molecules and proinflammatory cytokines (19). To test whether the requirement for NF-B1 expression in Th2 cell differentiation was intrinsic to the T cell lineage or whether NF-B1 can regulate APC function during a Th2 response, an adoptive transfer model in which purified NF-Bsufficient OVA-specific DO11.10 TCR Tg CD3 ϩ T cells were transferred into syngeneic WT or NF-B1 Ϫ/Ϫ recipients was used.…”

Section: Nf-b1 ϫ/ϫ Apc Fail To Promote Ag-specific Th2 Cell Differentmentioning

confidence: 99%

Dendritic Cell-Intrinsic Expression of NF-κB1 Is Required to Promote Optimal Th2 Cell Differentiation

Artis

Kane

Fiore

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

A number of receptors and signaling pathways can influence the ability of dendritic cells (DC) to promote CD4+ Th type 1 (Th1) responses. In contrast, the regulatory pathways and signaling events that govern the ability of DC to instruct Th2 cell differentiation remain poorly defined. In this report, we demonstrate that NF-κB1 expression within DC is required to promote optimal Th2 responses following exposure to Schistosoma mansoni eggs, a potent and natural Th2-inducing stimulus. Although injection of S. mansoni eggs induced production of IL-4, IL-5, and IL-13 in the draining lymph node of wild-type (WT) mice, NF-κB1−/− hosts failed to express Th2 cytokines and developed a polarized Ag-specific IFN-γ response. In an in vivo adoptive transfer model in which NF-κB-sufficient OVA-specific DO11.10 TCR transgenic T cells were injected into OVA-immunized WT or NF-κB1−/− hosts, NF-κB1−/− APCs efficiently promoted CD4+ T cell proliferation and IFN-γ responses, but failed to promote Ag-specific IL-4 production. Further, bone marrow-derived DC from NF-κB1−/− mice failed to promote OVA-specific Th2 cell differentiation in in vitro coculture studies. Last, S. mansoni egg Ag-pulsed NF-κB1−/− DC failed to prime for Th2 cytokine responses following injection into syngeneic WT hosts. Impaired Th2 priming by NF-κB1−/− DC was accompanied by a reduction in MAPK phosphorylation in Ag-pulsed DC. Taken together, these studies identify a novel requirement for DC-intrinsic expression of NF-κB1 in regulating the MAPK pathway and governing the competence of DC to instruct Th2 cell differentiation.

show abstract

Section: Nf-b1 ϫ/ϫ Apc Fail To Promote Ag-specific Th2 Cell Differentmentioning

confidence: 99%

Dendritic Cell-Intrinsic Expression of NF-κB1 Is Required to Promote Optimal Th2 Cell Differentiation

Artis

Kane

Fiore

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…This form of NF-κB is in fact the most abundant and common activator of both gene activation and viral transcription, out of all the homo-and heterodimers of the Rel family [34][35][36]. In most cases, the rapid degradation of the inhibitor protein IκB-α precedes NF-κB translocation.…”

Section: Discussionmentioning

confidence: 99%

Nf-κb-Dependent Inhibition of HIV-1 Transcription by Withaferin A

Shi¹,

Wilhelm²,

Bell³

et al. 2017

HIV Curr Res

View full text Add to dashboard Cite

Despite the remarkable progress made in suppressing HIV-1 infection, antiretroviral drugs are still often inaccessible in developing countries, and there is an urgent need for cheaper and alternative drugs. HIV-1 replication is triggered by the activation of the long terminal repeat (LTR) promoter, which contains two binding sites for the transcription factor nuclear factor κB (NF-κB). Withaferin A (WA), a steroidal lactone isolated from the Indian medicinal plant Withania somnifera, has been found to have significant pharmacological effects on the regulation of immune response. Recent studies have demonstrated that the anti-inflammatory properties of WA are mainly due to its inhibition of the NF-κB pathway. In the present study, we demonstrate that WA represses HIV-1 LTR transcription and viral replication through NF-κB inhibition.The human lymphocyte T cell line Jurkat E6.1 was treated with WA and infected with wild-type pseudotyped HIV-1 particles or mutant viruses containing inactive κB sites. Then, the effect of WA on HIV-1 replication was evaluated by the measurement of reporter activity. Electrophoretic mobility shift assays and Western blots analysis were also performed to study the impact of WA on NF-κB. We found that WA inhibited the transcription of wild-type pseudotyped viruses in single-round infection assays, whereas mutant viruses containing inactive κB sites showed a reduced response to WA. Moreover, we found that WA directly or indirectly inhibits NF-κB nuclear translocation, including RelA and p50 subunits. However, the degradation of inhibitory protein IκB-α was not prevented by WA. Taken together, our results suggest that WA inhibits HIV-1 transcription in human Jurkat E6.1 lymphocyte T cells through the NF-κB pathway.

show abstract

“…The downregulation by NMP on the NF-κB pathway has been rec- ognized in macrophages (Ghayor et al, 2015) and in osteoclasts . And the NF-κB pathway is indicated to regulate the expression of multiple genes involved in inflammatory and immune response (McKay and Cidlowski, 1999;Caamaño and Hunter, 2002). And the IKK (inhibitory κB (IκB) kinase)-mediated phosphorylation-induced proteasomal degradation of IκB inhibitor, enabling the active NF-κB to translocate to the nucleus (Vallabhapurapu and Karin, 2009).…”

Section: Discussionmentioning

confidence: 99%

N-methyl pyrrolidone (NMP) ameliorates the hypoxia-reduced osteoblast differentiation via inhibiting the NF-κB signaling

Zhao

et al. 2016

J. Toxicol. Sci.

View full text Add to dashboard Cite

-Ischemic-hypoxic condition for local osteoblasts and bone mesenchymal stem cells during bone fracture inhibits bone repairing. N-methyl pyrrolidone (NMP) has been approved as a safe and biologically inactive small chemical molecule, and might be useful for bone fracture repairing. In the present study, we investigated the effect of NMP on the hypoxia-reduced cellular viability and the expression of differentiation-associated markers, such as bone morphogenetic protein 2 (BMP-2), propeptide of type I procollagen I (PINP), alkaline phosphatase (ALP) or runt-related transcription factor 2 (Runx2) in the osteoblasts, and then we examined the molecular mechanism underlining such effect in the human osteoblastic hFOB 1.19 cells. Our results demonstrated that NMP significantly blocked the hypoxia-induced cell viability reduction and inhibited the hypoxia-caused expression downregulation of BMP-2, PINP, ALP and Runx2 in hFOB 1.19 cells. Then we confirmed the involvement of nuclear factor κB (NF-κB) pathway in the regulation by NMP on the hypoxia-mediated the reduction of osteoblast differentiation. The upregulated expression and transcriptional activity of NF-κB, while the downregulated inhibitory κB expression by the hypoxia treatment was reversed by the treatment with 10 mM NMP. In conclusion, our study found a protective role of NMP in osteoblast differentiation in response to hypoxia, and such protection was through inhibiting the NF-κB signaling. This suggests that NMP might be a protective agent in bone fracture repairing.

show abstract

NF-κB Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions

Cited by 462 publications

References 230 publications

Dendritic Cell-Intrinsic Expression of NF-κB1 Is Required to Promote Optimal Th2 Cell Differentiation

Dendritic Cell-Intrinsic Expression of NF-κB1 Is Required to Promote Optimal Th2 Cell Differentiation

Nf-κb-Dependent Inhibition of HIV-1 Transcription by Withaferin A

N-methyl pyrrolidone (NMP) ameliorates the hypoxia-reduced osteoblast differentiation via inhibiting the NF-κB signaling

Contact Info

Product

Resources

About