Differential mRNA Expression of Inflammatory Cytokines in Cultured Human Fetal Membrane Cells Responding to Influenza Virus Infection

Influenza is a significant health concern worldwide. Viral infection induces local and systemic activation of the immune system causing attendant changes in metabolism. High-resolution metabolomics (HRM) uses advanced mass spectrometry and computational methods to measure thousands of metabolites inclusive of most metabolic pathways. We used HRM to identify metabolic pathways and clusters of association related to inflammatory cytokines in lungs of mice with H1N1 influenza virus infection. Infected mice showed progressive weight loss, decreased lung function, and severe lung inflammation with elevated cytokines [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ] and increased oxidative stress via cysteine oxidation. HRM showed prominent effects of influenza virus infection on tryptophan and other amino acids, and widespread effects on pathways including purines, pyrimidines, fatty acids, and glycerophospholipids. A metabolome-wide association study (MWAS) of the aforementioned inflammatory cytokines was used to determine the relationship of metabolic responses to inflammation during infection. This cytokine-MWAS (cMWAS) showed that metabolic associations consisted of distinct and shared clusters of 396 metabolites highly correlated with inflammatory cytokines. Strong negative associations of selected glycosphingolipid, linoleate, and tryptophan metabolites with IFN-γ contrasted strong positive associations of glycosphingolipid and bile acid metabolites with IL-1β, TNF-α, and IL-10. Anti-inflammatory cytokine IL-10 had strong positive associations with vitamin D, purine, and vitamin E metabolism. The detailed metabolic interactions with cytokines indicate that targeted metabolic interventions may be useful during life-threatening crises related to severe acute infection and inflammation.

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Association of influenza virus infection and inflammatory cytokines with acute myocardial infarction

Inflammation Research ◽

10.1007/s00011-012-0449-3 ◽

2012 ◽

Vol 61 (6) ◽

pp. 591-598 ◽

Cited By ~ 35

Author(s):

Xiuru Guan ◽

Wei Yang ◽

Xijuan Sun ◽

Lanfeng Wang ◽

Benjiang Ma ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Influenza Virus ◽

Virus Infection ◽

Inflammatory Cytokines ◽

Influenza Virus Infection

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Current Status of Monocyte Differentiation-Inducing (MDI) Factors Derived from Human Fetal Membrane Chorion Cells Undergoing Apoptosis after Influenza Virus Infection

Gene Regulation and Systems Biology ◽

10.4137/grsb.s374 ◽

2007 ◽

Vol 1 ◽

pp. GRSB.S374 ◽

Cited By ~ 2

Author(s):

Noboru Uchide ◽

Hiroo Toyoda

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Current Status ◽

Fetal Membrane ◽

Monocyte Differentiation

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Possible Roles of Proinflammatory and Chemoattractive Cytokines Produced by Human Fetal Membrane Cells in the Pathology of Adverse Pregnancy Outcomes Associated with Influenza Virus Infection

Mediators of Inflammation ◽

10.1155/2012/270670 ◽

2012 ◽

Vol 2012 ◽

pp. 1-32 ◽

Cited By ~ 34

Author(s):

Noboru Uchide ◽

Kunio Ohyama ◽

Toshio Bessho ◽

Makoto Takeichi ◽

Hiroo Toyoda

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Proinflammatory Cytokines ◽

Pregnancy Outcomes ◽

Influenza Virus Infection ◽

Adverse Pregnancy Outcomes ◽

Fetal Membrane ◽

Premature Delivery ◽

Fetal Membranes ◽

Adverse Pregnancy

Pregnant women are at an increased risk of influenza-associated adverse outcomes, such as premature delivery, based on data from the latest pandemic with a novel influenza A (H1N1) virus in 2009-2010. It has been suggested that the transplacental transmission of influenza viruses is rarely detected in humans. A series of our study has demonstrated that influenza virus infection induced apoptosis in primary cultured human fetal membrane chorion cells, from which a factor with monocyte differentiation-inducing (MDI) activity was secreted. Proinflammatory cytokines, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-β, were identified as a member of the MDI factor. Influenza virus infection induced the mRNA expression of not only the proinflammatory cytokines but also chemoattractive cytokines, such as monocyte chemoattractant protein (MCP)-1, regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1β, IL-8, growth-regulated oncogene (GRO)-α, GRO-β, epithelial cell-derived neutrophil-activating protein (ENA)-78, and interferon inducible protein (IP)-10 in cultured chorion cells. These cytokines are postulated to associate with human parturition. This paper, therefore, reviews (1) lessons from pandemic H1N1 2009 in pregnancy, (2) production of proinflammatory and chemoattractive cytokines by human fetal membranes and their functions in gestational tissues, and (3) possible roles of cytokines produced by human fetal membranes in the pathology of adverse pregnancy outcomes associated with influenza virus infection.

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Characterization of monocyte differentiation-inducing (MDI) factors derived from human fetal membrane chorion cells undergoing apoptosis after influenza virus infection

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2006.05.014 ◽

2006 ◽

Vol 38 (11) ◽

pp. 1926-1938 ◽

Cited By ~ 6

Author(s):

Noboru Uchide ◽

Chiho Tadera ◽

Hiroko Sarai ◽

Kunio Ohyama ◽

Toshio Bessho ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Virus Infection ◽

Fetal Membrane ◽

Monocyte Differentiation

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Oral Supplementation of the Vitamin D Metabolite 25(OH)D3 Against Influenza Virus Infection in Mice

Nutrients ◽

10.3390/nu12072000 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2000

Author(s):

Hirotaka Hayashi ◽

Masatoshi Okamatsu ◽

Honami Ogasawara ◽

Naoko Tsugawa ◽

Norikazu Isoda ◽

...

Keyword(s):

Vitamin D ◽

Influenza Virus ◽

Virus Infection ◽

Inflammatory Cytokines ◽

Influenza A ◽

Clinical Manifestations ◽

Influenza Virus Infection ◽

High Dose ◽

Oral Supplementation ◽

Hydroxyvitamin D

Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)2D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D3 [25(OH)D3], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D3 and were challenged with the influenza virus. In the lungs of 25(OH)D3-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D3-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D3 suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model.

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Diallyl Trisulfide Protects Against H9N2 Avian Influenza Virus Infection

10.21203/rs.3.rs-295808/v1 ◽

2021 ◽

Author(s):

Le Ming ◽

Zhihui Li ◽

Xiaofang Li ◽

Ling Tang ◽

Guimei He

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Inflammatory Cytokines ◽

Influenza Virus Infection ◽

H9n2 Virus ◽

Diallyl Trisulfide ◽

H9n2 Avian Influenza Virus ◽

Tnf Α

Abstract BackgroundDiallyl trisulfide is a component of garlic. It has been shown to have anti-fungus, anti-cancer, and anti-virus activities. We hypothesized that diallyl trisulfide can enhance host defense mechanisms against the infection by influenza virus A subtype H9N2, which is the most prevalent subtype of influenza viruses in poultry in many countries in Asia.MethodsIn this study, the effects of diallyl trisulfide on influenza virus will be investigated in vivo and in vitro respectively. The expression levels of IL-6, TNF-α, RIG-I, IRF-3, IFN-β, and H9N2 avian influenza virus M gene were detected using Quantitative real-time RT-PCR.ResultsIn vitro, we found that treatment of A549 cells before or after H9N2 virus infection resulted in reduced viral loads, increased expression of antiviral genes (RIG-I, IRF-3 and interferon-β), and decreased expression of inflammatory cytokines (TNF-α and IL-6). These effects were also observed in H9N2 virus infected mice. ConclusionsThese results suggest that diallyl trisulfide inhibits H9N2 virus replication and down regulate the expression of inflammatory cytokines. Also this research indicates that diallyl trisulfide might be a kind of effective drug against influenza virus infection.

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