The fungal metabolite, citrinin, inhibits lipopolysaccharide/interferon-γ-induced nitric oxide production in glomerular mesangial cells

Liu, Biing-Hui; Chi, Jhih-Ying; Hsiao, Yu-Wei; Tsai, Kuen-Daw; Lee, Yi‐Ju; Lin, Chung-Saint; Hsu, Shu-Shong; Yang, Shumei; Lin, Ting‐Hui

doi:10.1016/j.intimp.2010.09.017

Cited by 16 publications

(5 citation statements)

References 35 publications

(65 reference statements)

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“…This was associated with a significant decrease in the expressions of pro-inflammatory cytokines and a high correlation between them, which was significant for the expression of IFN-γ. A significant reduction in the translocation of NF-κB has also been demonstrated by treatments with other mycotoxins, gliotoxins in lipopolysaccharide-stimulated dendritic cells (DC) ( 66 , 67 ) and citrinin in MES-13 cells, followed by the suppression of the expressions of IFN-γ, NO and inducible NO synthase ( 68 ) . No effect on the expression of NF-κB was observed on treatment with patulin in lipopolysaccharide-stimulated DC ( 66 ) .…”

Section: Discussionmentioning

confidence: 92%

Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

et al. 2013

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Zearalenone (ZEA) is an oestrogenic mycotoxin produced by Fusarium species, considered to be a risk factor from both public health and agricultural perspectives. In the present in vivo study, a feeding trial was conducted to evaluate the in vivo effect of a ZEA-contaminated diet on immune response in young pigs. The effect of ZEA on pro-inflammatory (TNF-a, IL-8, IL-6, IL-1b and interferon-g) and antiinflammatory (IL-10 and IL-4) cytokines and other molecules involved in inflammatory processes (matrix metalloproteinases (MMP)/ tissue inhibitors of matrix metalloproteinases (TIMP), nuclear receptors: PPARg and NF-kB1, mitogen-activated protein kinases (MAPK): mitogen-activated protein kinase kinase kinase 7 (TAK1)/mitogen-activated protein kinase 14 (p38a)/mitogen-activated protein kinase 8 ( JNK1)/ mitogen-activated protein kinase 9 ( JNK2)) in the liver of piglets was investigated. The present results showed that a concentration of 316 parts per billion ZEA leads to a significant decrease in the levels of pro-and anti-inflammatory cytokines at both gene expression and protein levels, correlated with a decrease in the levels of other inflammatory mediators, MMP and TIMP. The results also showed that dietary ZEA induces a dramatic reduction in the expressions of NF-kB1 and TAK1/p38a MAPK genes in the liver of the experimentally intoxicated piglets, and has no effect on the expression of PPARg mRNA. The present results suggest that the toxic action of ZEA begins in the upstream of the MAPK signalling pathway by the inhibition of TAK1, a MAPK/NF-kB activator. In conclusion, the present study shows that ZEA alters several important parameters of the hepatic cellular immune response. From an economic point of view, these data suggest that, in pigs, ZEA is not only a powerful oestrogenic mycotoxin but also a potential hepatotoxin when administered through the oral route. Therefore, the present results represent additional data from cellular and molecular levels that could be taken into account in the determination of the regulation limit of the tolerance to ZEA.

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Section: Discussionmentioning

confidence: 92%

Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

et al. 2013

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“…Quantitative real-time PCR was finished with Roche Cyber Green PCR mix kit on Biorad C1000 Thermal Cycler. The primer pairs for RT-PCR were as follows: gapdh forward 5′-TGGCAAATTCCATGGCAC-3′, reverse 5′-CCATGGTGGTGAAGACGC-3′; socs3 forward 5′-CCATGGTGGTGAAGACGC-3′, reverse 5′-CCTGTCCAGCCCAATACCTGA-3′ [27]; IRF-1 forward5′-CGATACAAAGCAGGGGAAAA-3′, reverse 5′-TAGCTGCTGTGGTCATCAGG-3′ [28].…”

Section: Methodsmentioning

confidence: 99%

Brevilin A, a Novel Natural Product, Inhibits Janus Kinase Activity and Blocks STAT3 Signaling in Cancer Cells

Chen

Jing

et al. 2013

PLoS ONE

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Signal abnormalities in human cells usually cause unexpected consequences for individual health. We focus on these kinds of events involved in JAK-STAT signal pathways, especially the ones triggered by aberrant activated STAT3, an oncoprotein which participates in essential processes of cell survival, growth and proliferation in many types of tumors, as well as immune diseases. By establishing a STAT3 signal based high-throughput drug screening system in human lung cancer A549 cells, we have screened a library from natural products which contained purified compounds from medicinal herbs. One compound, named Brevilin A, exhibited both strong STAT3 signal inhibition and STAT3 signal dependent cell growth inhibition. Further investigations revealed that Brevilin A not only inhibits STAT3 signaling but also STAT1 signaling for cytokines induced phosphorylation of STAT3 and STAT1 as well as the expression of their target genes. In addition, we found Brevilin A could attenuate the JAKs activity by blocking the JAKs tyrosine kinase domain JH1. The levels of cytokine induced phosphorylation of STATs and other substrates were dramatically reduced by treatment of Brevilin A. The roles of Brevilin A targeting on JAKs activity indicate that Brevilin A may not only be used as a STAT3 inhibitor but also a compound blocking other JAK-STAT hyperactivation. Thus, these findings provided a strong impetus for the development of selective JAK-STAT inhibitors and therapeutic drugs in order to improve survival of patients with hyperactivated JAKs and STATs.

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“…Pe. chrysogenum ’s impact on both parasitic and bacterial infection suggests that it involves the suppression of a physiological system of the mosquito that can act against both bacteria and the parasite, such as the innate immune system 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 . Alternatively, the fungus-produced factor could enhance a mosquito physiological system that favors both parasitic and bacterial infection.…”

Section: Resultsmentioning

confidence: 99%

“…A recent study showed that a Anopheles -associated yeast strain produced an antiparasitic toxin 10 . Fungi produce an extensive range of proteins and secondary metabolites, making them attractive sources for the discovery of novel bioactive molecules with desirable properties 11 12 . Here we report the isolation of a commonly mosquito-associated ascomycete fungus, Penicillium chrysogenum , from the midgut of field-collected Anopheles mosquitoes.…”

mentioning

confidence: 99%

A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection

Angleró-Rodríguez

Blumberg

Dong

et al. 2016

Sci Rep

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Whereas studies have extensively examined the ability of bacteria to influence Plasmodium infection in the mosquito, the tripartite interactions between non-entomopathogenic fungi, mosquitoes, and Plasmodium parasites remain largely uncharacterized. Here we report the isolation of a common mosquito-associated ascomycete fungus, Penicillium chrysogenum, from the midgut of field-caught Anopheles mosquitoes. Although the presence of Pe. chrysogenum in the Anopheles gambiae midgut does not affect mosquito survival, it renders the mosquito significantly more susceptible to Plasmodium infection through a secreted heat-stable factor. We further provide evidence that the mechanism of the fungus-mediated modulation of mosquito susceptibility to Plasmodium involves an upregulation of the insect’s ornithine decarboxylase gene, which sequesters arginine for polyamine biosynthesis. Arginine plays an important role in the mosquito’s anti-Plasmodium defense as a substrate of nitric oxide production, and its availability therefore has a direct impact on the mosquito’s susceptibility to the parasite. While this type of immunomodulatory mechanism has already been demonstrated in other host-pathogen interaction systems, this is the first report of a mosquito-associated fungus that can suppress the mosquito’s innate immune system in a way that would favor Plasmodium infection and possibly malaria transmission.

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The fungal metabolite, citrinin, inhibits lipopolysaccharide/interferon-γ-induced nitric oxide production in glomerular mesangial cells

Cited by 16 publications

References 35 publications

Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

Natural feed contaminant zearalenone decreases the expressions of important pro- and anti-inflammatory mediators and mitogen-activated protein kinase/NF-κB signalling molecules in pigs

Brevilin A, a Novel Natural Product, Inhibits Janus Kinase Activity and Blocks STAT3 Signaling in Cancer Cells

A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection

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