Two NF-κB inhibitor-alpha (IκBα) genes from rock bream (Oplegnathus fasciatus): Molecular characterization, genomic organization and mRNA expression analysis after immune stimulation

Lee, Jehee; Umasuthan, Navaneethaiyer; Whang, Ilson; Revathy, Kasthuri Saranya; Lee, Sukkyoung; Zoysa, Mahanama De; Oh, Chulhong; Kang, Do‐Hyung; Noh, Jae Koo

doi:10.1016/j.fsi.2014.10.015

Cited by 17 publications

(11 citation statements)

References 49 publications

(56 reference statements)

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“…Another possible regulation of anti-inflammatory effects of TRP is by inhibiting the degradation of IκBα 34 . The inhibitory molecule IκBα sequesters NF-κB in an inactivate form in the cytoplasm and blocks its translocation to the nucleus 35 , leading to an absent positive feedback for further TNF-α production. Table 3.…”

Section: Discussionmentioning

confidence: 99%

Tryptanthrin promotes keratinocyte and fibroblast responses in vitro after infection with Trichophyton benhamiae DSM6916

Hesse-Macabata

Morgner

Elsner

et al. 2020

Sci Rep

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Exceedingly virulent pathogens and growing antimicrobial resistances require new therapeutic approaches. The zoophilic dermatophyte Trichophyton benhamiae causes highly inflammatory, cutaneous fungal infections. Recently, it could be shown that the plant-derived alkaloid tryptanthrin (TRP) exhibits strong anti-microbial activities against yeasts and dermatophytes. The aim of this study was to analyse the bioactivity of TRP under infectious conditions using an in-vitro dermatophytosis model employing fibroblasts and keratinocytes infected with T. benhamiae DSM6916. Analyses comprised determination of cell viability, effects on the innate immune response including expression and secretion of pro-inflammatory cytokines/chemokines as well as expression of various antimicrobial peptides (AMP), toll-like receptor (TLR) 2 and proliferation marker MKI67. T. benhamiae caused severe inflammation in the cutaneous cell models. TRP almost fully prevented T. benhamiae-derived damage of dermal fibroblasts and substantially reduced it in epidermal keratinocytes. A distinct down-regulation of the expression and secretion of pro-inflammatory cytokines was observed. Further, TRP promoted AMP expression, especially of HBD2 and HBD3, in keratinocytes even without fungal presence. This study provides crucial evidence that TRP is not only a strong antifungal agent but also potentially modulates the innate immune response. This makes it interesting as a natural antimycotic drug for adjuvant treatment and prevention of fungal re-infection. Dermatophytoses present a serious public health issue affecting 20-25% of the world's population 1. Especially zoophilic dermatophytes often cause acute, highly inflammatory, cutaneous infections in humans 2,3. In Germany the guinea pig-associated dermatophyte Trichophyton benhamiae pertain to one of the most common cause for fungal infections especially among children and adolescents 4,5. Due to the growing mobility and migration, a pathogen shift with an emergent incidence of new fungi can be observed 6 , which in turn leads to an increasing application of broad-spectrum antimycotics. A new more virulent and potentially contagious Trichophyton mentagrophytes strain was recently isolated in India. Its origin seems to be unknown, but its occurrence is dramatically on the rise even replacing T. rubrum as the most common species causing superficial dermatophytosis in India 7,8. With the rising prevalence of fungal infections, the emerging antimycotic resistance 9,10 as well as the appearance of new and highly virulent pathogens novel therapeutic approaches are required. Hence, it is of great interest to find alternative, natural, antimycotically effective agents. In addition to exhibiting antimicrobial properties, it would be worthwhile if they also potentially influenced the immune response by e.g. promoting the defence and immune responses of cells against invading pathogens. Plants possess secondary metabolites that are anti-microbial compounds accumulating in regions of pathogenic infection. These in...

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Section: Discussionmentioning

confidence: 99%

Tryptanthrin promotes keratinocyte and fibroblast responses in vitro after infection with Trichophyton benhamiae DSM6916

Hesse-Macabata

Morgner

Elsner

et al. 2020

Sci Rep

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“…Furthermore, our previous studies have also demonstrated that the antiinflammatory effects of propofol were mediated by apoM in cardiovascular diseases (Ma et al, 2013). ICAM-1 and VCAM-1 were one kind of important proinflammatory molecules and could be markedly induced by the TNF-a in inflammation (Osborn et al, 1989;Chen et al, 1995;Lee et al, 2015;Paulsen et al, 2015). In this study, our findings showed that the apoM could significantly downregulate TNF-a-induced expression of VCAM-1 and ICAM-1 through inhibiting the activity of NF-kB in HepG2 cells.…”

Section: Discussionmentioning

confidence: 97%

“…Luo et al (2004) demonstrated that the human apoM gene was located in p21.31 on chromosome 6, a region in which many genes were linked to immune and inflammatory responses. It is widely recognized that the inflammation could increase the risk of developing cardiovascular diseases such as atherosclerosis (Lee et al, 2014). As one kind of apoprotein, apoM is closely associated with the mechanism of HDL-mediated antiatherosclerosis (Xu et al, 1999;Hu et al, 2010;Kardassis et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…As one kind of cell adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were highly expressed in human endothelial cells and could be markedly induced by the TNF-a in inflammation (Osborn et al, 1989;Lee et al, 2015;Paulsen et al, 2015). Accumulating evidence suggested that the increasing levels of ICAM-1 and VCAM-1 could contribute to the recruitment of inflammatory cells at the sites of inflammation and cell-mediated immune responses (Chen et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

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ApoM Suppresses TNF-α-Induced Expression of ICAM-1 and VCAM-1 Through Inhibiting the Activity of NF-κB

Gao

Wang

et al. 2015

DNA and Cell Biology

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To explore the anti-inflammatory effect of apolipoprotein M (apoM) on regulation of tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and further investigate the molecular mechanism of apoM in this process. We found that TNF-α could decrease expression of apoM and inhibitor of NF-κB-α (IκBα) in HepG2 cells. Overexpression of apoM caused a significant decrease of ICAM-1 and VCAM-1 expression, while it caused a significant increase of IκBα expression in HepG2 cells. Furthermore, the treatment with TNF-α could increase ICAM-1 and VCAM-1 expression, decrease IκBα protein expression, and increase nuclear factor-κB (NF-κB) activity, and these effects were markedly enhanced by small interfering RNA (siRNA)-mediated silencing of apoM in HepG2 cells. Our findings demonstrated that apoM suppressed TNF-α-induced expression of ICAM-1 and VCAM-1 through inhibiting the activity of NF-κB.

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“…NF-kappa-B inhibitor alpha (S. salar) is both up- and down-regulated and inhibits NF-kappa-B as mediator impacting processes such as apoptosis, proliferation, differentiation, and development ( Lee et al, 2014 ). Then, in SW1 fish NF-kappa-B activity is inhibited while in SW2 fish NF-kappa-B activity is stimulated.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Effects of Dietary Seaweeds in LPS Challenged Atlantic Salmon Salmo salar as Determined by Deep RNA Sequencing of the Head Kidney Transcriptome

et al. 2018

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Seaweeds may represent immuno-stimulants that could be used as health-promoting fish feed components. This study was performed to gain insights into the immunomodulatory effects of dietary seaweeds in Atlantic salmon. Specifically tested were 10% inclusion levels of Laminaria digitata (SW1) and a commercial blend of seaweeds (Oceanfeed®) (SW2) against a fishmeal based control diet (FMC). Differences between groups were assessed in growth, feed conversion ratio and blood parameters hematocrit and hemoglobin. After a LPS challenge of fish representing each of the three groups, RNAseq was performed on the head kidney as major immune organ to determine transcriptomic differences in response to the immune activation. Atlantic salmon fed with dietary seaweeds did not show major differences in performance in comparison with fishmeal fed fish. RNAseq resulted in ∼154 million reads which were mapped against a NCBI Salmo salar reference and against a de novo assembled S. salar reference for analyses of expression of immune genes and ontology of immune processes among the 87,600 cDNA contigs. The dietary seaweeds provoked a more efficient immune response which involved more efficient identification of the infection site, and processing and presentation of antigens. More specifically, chemotaxis and the chemokine-mediated signaling were improved and therewith the defense response to Gram-positive bacterium reduced. Specific Laminaria digitata effects included reduction of the interferon-gamma-mediated signaling. Highly upregulated and specific for this diet was the expression of major histocompatibility complex class I-related gene protein. The commercial blend of seaweeds caused more differential expression than Laminaria digitata and improved immune processes such as receptor-mediated endocytosis and cell adhesion, and increased the expression of genes involved in response to lipopolysaccharide and inflammatory response. Particularly, expression of many important immune receptors was up-regulated illustrating increased responsiveness. NF-kappa-B inhibitor alpha is an important gene that marked the difference between both seaweed diets as Laminaria digitata inhibits the expression for this cytokine while the blend of seaweeds stimulates it. It can be concluded that the inclusion of seaweeds such as Laminaria digitata can have important modulatory effects on the immune capacity of Atlantic salmon resulting in a more efficient immune response.

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Two NF-κB inhibitor-alpha (IκBα) genes from rock bream (Oplegnathus fasciatus): Molecular characterization, genomic organization and mRNA expression analysis after immune stimulation

Cited by 17 publications

References 49 publications

Tryptanthrin promotes keratinocyte and fibroblast responses in vitro after infection with Trichophyton benhamiae DSM6916

Tryptanthrin promotes keratinocyte and fibroblast responses in vitro after infection with Trichophyton benhamiae DSM6916

ApoM Suppresses TNF-α-Induced Expression of ICAM-1 and VCAM-1 Through Inhibiting the Activity of NF-κB

Immunomodulatory Effects of Dietary Seaweeds in LPS Challenged Atlantic Salmon Salmo salar as Determined by Deep RNA Sequencing of the Head Kidney Transcriptome

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