Identification of IκBα in Japanese eel Anguilla japonica that impairs the IKKα-dependent activation of NF-κB, AP1, and type I IFN signaling pathways

Feng, Jia; Xu, Yuankai; Lin, Peng; Peng, Xinwei; Wang, Yilei; Zhang, Ziping

doi:10.1016/j.dci.2021.104044

Cited by 12 publications

(7 citation statements)

References 49 publications

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“…AP-1, a key downstream target of the MAPK signaling pathway, regulates the expression of many cytokines including TNFα, IL-6, IL1 and plays a key role in the innate immune response (30). In accordance with this, our study showed signi cantly increased plasma IL-6 levels in the BS-Z15 secondary metabolite treatment group and activation of the tumor necrosis factor signaling pathway.…”

Section: Discussionsupporting

confidence: 87%

Effect of Bacillus subtilis strain Z15 secondary metabolites on immune function in mice

Cao

Yang

Zhao

et al. 2022

Preprint

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Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved NK cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased plasma levels of IFN-γ, IL-6, IgG and IgM. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes terms for immune-related entries and pathways such as TNF and TLR signaling pathways, and upregulated expression levels of immune-related genes such as C1qb, C4b, TCR and RFX5. BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

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Section: Discussionsupporting

confidence: 87%

Effect of Bacillus subtilis strain Z15 secondary metabolites on immune function in mice

Cao

Yang

Zhao

et al. 2022

Preprint

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“…These tissue-specific expression patterns obviously vary in different fish species, as demonstrated at least for nfkbia . The prominent nfkbia transcript level in the spleen of rainbow trout is in line with findings in the Japanese eel Anguilla japonica [ 63 ] and the mandarin fish Siniperca chuatsi [ 64 ], but it contrasts with the rather low splenic expression in the rock bream O. fasciatus [ 55 ], the blunt snout bream M. amblycephala [ 59 ] or the half-smooth tongue sole Cynoglossus semilaevis [ 60 ]. No comparable datasets are presently available for the expression profiles of the other nfkbi transcripts.…”

Section: Discussionsupporting

confidence: 80%

“…However, a detailed characterisation of the iκb proteins from lower vertebrates is still pending. Iκbα is the best researched iκb ortholog and has been characterised in different fish species [ 53 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ], whereas its iκbβ paralog has apparently been lost in various bony fish families. According to the gene database of the National Center for Biotechnology Information (NCBI), the iκbβ-encoding nfkbib gene is absent from the sequenced genomes of the Salmonidae, Percidae, Gadidae, Carangidae, and Oryziinae, although it is still present in other teleost fish species from the Cyprinidae or Ictaluridae (as of December 2022).…”

Section: Introductionmentioning

confidence: 99%

Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish

van Muilekom,

Collet,

Rebl

et al. 2023

IJMS

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NF-κB signalling is largely controlled by the family of ‘inhibitors of NF-κB’ (IκB). The relevant databases indicate that the genome of rainbow trout contains multiple gene copies coding for iκbα (nfkbia), iκbε (nfkbie), iκbδ (nkfbid), iκbζ (nfkbiz), and bcl3, but it lacks iκbβ (nfkbib) and iκbη (ankrd42). Strikingly, three nfkbia paralogs are apparently present in salmonid fish, two of which share a high sequence identity, while the third putative nfkbia gene is significantly less like its two paralogs. This particular nfkbia gene product, iκbα, clusters with the human IκBβ in a phylogenetic analysis, while the other two iκbα proteins from trout associate with their human IκBα counterpart. The transcript concentrations were significantly higher for the structurally more closely related nfkbia paralogs than for the structurally less similar paralog, suggesting that iκbβ probably has not been lost from the salmonid genomes but has been incorrectly designated as iκbα. In the present study, two gene variants coding for iκbα (nfkbia) and iκbε (nfkbie) were prominently expressed in the immune tissues and, particularly, in a cell fraction enriched with granulocytes, monocytes/macrophages, and dendritic cells from the head kidney of rainbow trout. Stimulation of salmonid CHSE-214 cells with zymosan significantly upregulated the iκbα-encoding gene while elevating the copy numbers of the inflammatory markers interleukin-1-beta and interleukin-8. Overexpression of iκbα and iκbε in CHSE-214 cells dose-dependently quenched both the basal and stimulated activity of an NF-κB promoter suggesting their involvement in immune-regulatory processes. This study provides the first functional data on iκbε—versus the well-researched iκbα factor—in a non-mammalian model species.

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“…IFN-β enhances the immune response, activating the innate and adaptive immune responses and inhibiting viral infection and replication [ 33 ]. AP-1, a key downstream target of the MAPK signaling pathway, regulates the expression of many cytokines including TNFα, IL-6, IL1 and plays a key role in the innate immune response [ 34 ]. Upregulation of CCL3 expression enhances the release of innate immune cells (e.g., NK cells and DCs) from bone marrow into the blood, mobilizes NK cells to produce IFNγ, and increases the level of IFNγ in the blood of mice, which is consistent with the significant increase in the level of IFN-γ in the blood of mice in the BS-Z15 secondary metabolite treatment group.…”

Section: Discussionmentioning

confidence: 99%

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice

Cao,

Aimaier,

Yang

et al. 2023

BMC Genomics

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Background Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. Results The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). Conclusions BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

show abstract

Identification of IκBα in Japanese eel Anguilla japonica that impairs the IKKα-dependent activation of NF-κB, AP1, and type I IFN signaling pathways

Cited by 12 publications

References 49 publications

Effect of Bacillus subtilis strain Z15 secondary metabolites on immune function in mice

Effect of Bacillus subtilis strain Z15 secondary metabolites on immune function in mice

Lost and Found: The Family of NF-κB Inhibitors Is Larger than Assumed in Salmonid Fish

Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice

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