Immune differentiation regulator p100 tunes NF-κB responses to TNF

Chatterjee, B. B.; Roy, Payel; Sarkar, Uday Aditya; Ratra, Yashika; Chawla, M. L.; Gomes, James; Basak, Soumen

doi:10.1101/414425

Cited by 2 publications

(2 citation statements)

References 46 publications

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“…Additionally, we observed that most of the genes in the adipocytokine signaling pathway have changed to varying degrees, and these genes are closely related to the NF-κB and MAPK signaling pathways. The NF-κB signaling pathway related genes TNF-α and FATCD36 are both decreased [33,34]. In addition, the transcription levels of STAT3, AMPK, Pgc-1α and Cpt1 are all increased (Fig.…”

Section: Discussionmentioning

confidence: 90%

Nitrogen-Doped Multiwalled Carbon Nanotubes Inhibit Fat Deposition via Immunomodulatory Actions

Xiao²,

et al. 2021

Preprint

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Multiwalled carbon nanotubes (MWCNTs) offer immense opportunities to deliver drug and biomolecules to targeted tissues. However, it’s unclear for us about their effects on fat metabolism. Here, we demonstrate that nitrogen-doped carboxylate-functionalized MWCNTs (N-MWCNTs) inhibit fat deposition both in vivo and in vitro primarily by suppressing adipogenesis. N-MWCNTs show good biocompatability in HEK293 mammalian cells. Intramuscular administration of N-MWCNTs does not affect the body weight gain and feed intake of mice, but reduces the fat mass. In in vitro-cultured adipocytes, N-MWCNTs suppress fat accumulation, accompanying with decreased and increased expression of adipogenic and lipolysis genes, respectively. Transcriptome analysis further certified the N-MWCNT alteration of fat metabolism-related genes. Interestingly, we observed the phagocytosis of N-MWCNTs by macrophage-like cells via TEM imaging. The mRNA sequencing data also showed remarkable variation of the genes involved in TLRs pathway, ultimately leading to down- or up-regulation of inflammatory factors, of which Tnfα, Il1, Il7, Il10, and Il12 are decreased, whereas Il6 and Il11 are increased. In conclusion, N-MWCNTs induce the production of inflammatory cytokines through immune responses, which trigger the reduction of fat deposition. These findings support the usage of N-MWCNTs as a promising delivery for anti-obesity agents.

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Section: Discussionmentioning

confidence: 90%

Nitrogen-Doped Multiwalled Carbon Nanotubes Inhibit Fat Deposition via Immunomodulatory Actions

Xiao²,

et al. 2021

Preprint

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“…The Relb promoter possesses a κB site, which directs RelA driven transcription, as well as a vitamin D receptor element (VDRE), which instructs vitamin D sensitive gene expression (Bren et al, 2001;Dong et al, 2003). Indeed, it was shown that the canonical RelA/NF-κB pathway is important for both basal as well as cytokine-induced expressions of RelB mRNA (Basak et al, 2008;Chatterjee et al, 2019). In contrast, vitamin D treatment caused Histone deacetylase 3 dependent transcriptional repression of Relb in dendritic cells (Dong et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

A vitamin D-RelB/NF-κB pathway limits Chandipura virus multiplication by rewiring the homeostatic state of autoregulatory type 1 interferon-IRF7 signaling

Ratra

Kumar

Saha

et al. 2021

Preprint

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Besides its functions in the skeletomuscular system, vitamin D also promotes protective immunity against viral pathogens. Viral sensing by mammalian cells triggers nuclear activation of RelA/NF-κB and IRF3 factors, which collaborate in mediating the early induction of antiviral type 1 interferons (T1-IFNs). Autocrine T1-IFN signaling further accumulates otherwise negligibly expressed IRF7 in virus-infected cells that then sustains T1-IFN production in a positive feedback. Surprisingly, prior cell-culture studies revealed that vitamin D actually suppresses signal-induced RelA activation. Indeed, it remains unclear how vitamin D limits viral multiplication in a cell-autonomous manner. Here, we examined the role of vitamin D in controlling cellular infections by the Chandipura virus (CHPV), a cytoplasmic RNA virus implicated in human epidemics. We found that vitamin D conditioning produced an altered cell state less permissive for CHPV multiplication because of the heightened expression of T1-IFNs. It is thought that viruses also induce a distinct RelB/NF-κB activity, which counteracts RelA-driven T1-IFN expressions in infected cells. Our analyses instead characterized a basal nuclear RelB activity, which was downregulated upon vitamin D-mediated suppression of RelB synthesis. Interestingly, this vitamin D-RelB pathway provoked IRF7-mediated positive autoregulation augmenting constitutive T1-IFN expressions even in the absence of viral infections. Accordingly, RelB deficiency rendered redundant, while IRF7 depletion abrogated antiviral vitamin D actions. In sum, our study suggests that the homeostatic state of the signaling circuitry comprising of the NF-κB and T1-IFN pathways connects micronutrients to antiviral immunity at the cellular level.Significance statementVitamin D limits viral infections, but the underlying mechanism remains unclear. Linking micronutrients to antiviral immunity, Ratra et al. characterize an immune signaling circuitry engaged by vitamin D that generates a cellular state less permissive to infections by Chandipura virus, a pathogen of public health importance.

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Immune differentiation regulator p100 tunes NF-κB responses to TNF

Cited by 2 publications

References 46 publications

Nitrogen-Doped Multiwalled Carbon Nanotubes Inhibit Fat Deposition via Immunomodulatory Actions

Nitrogen-Doped Multiwalled Carbon Nanotubes Inhibit Fat Deposition via Immunomodulatory Actions

A vitamin D-RelB/NF-κB pathway limits Chandipura virus multiplication by rewiring the homeostatic state of autoregulatory type 1 interferon-IRF7 signaling

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