Human rhinovirus serotypes induces different immune responses

Abstract Background Different species of human rhinovirus (HRV) can induce varied antiviral and inflammatory responses in human blood macrophages and lower airway epithelium. Although human nasal epithelial cells (HNECs) are a primary infection route of HRV, differences between major and minor groups of HRV in the upper airway epithelium have not been studied in detail. In this study, we investigated viral replications and immune responses of major and minor groups of HRV in the HNECs. Methods Viral replication, immune responses of IFN-β, IFN-λ, proinflammatory cytokines, and viral receptors, and mRNA expression of transcription factors of HRV16 (major group) and HRV1B (minor group) in the HNECs were assessed. Results Compared with HRV16, HRV1B replicated more actively without excessive cell death and produced higher IFN-β, IFN-λ1/3, CXCL10, IL-6, IL-8, and IL-18 levels. Furthermore, low-density lipoprotein receptor (LDLR), TLR3, MDA5, NF-κB, STAT1, and STAT2 mRNA levels increased in HRV1B-infected HNECs. Conclusion HRV1B induces a stronger antiviral and inflammatory response from cell entry to downstream signaling compared with HRV16.

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Scutellaria baicalensis Alleviates Insulin Resistance in Diet-Induced Obese Mice by Modulating Inflammation

International Journal of Molecular Sciences ◽

10.3390/ijms20030727 ◽

2019 ◽

Vol 20 (3) ◽

pp. 727 ◽

Cited By ~ 5

Author(s):

Hyun-Young Na ◽

Byung-Cheol Lee

Keyword(s):

Insulin Resistance ◽

Inflammatory Responses ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Postprandial Glucose ◽

Scutellaria Baicalensis ◽

Necrosis Factor Alpha ◽

Insulin Resistant ◽

The Metabolic Syndrome ◽

Epididymal Fat

Insulin resistance is strongly associated with the metabolic syndrome, and chronic inflammation is known to be a major mechanism of insulin resistance and is a therapeutic target. This study was designed to evaluate the effect of Scutellaria baicalensis (SB) in high-fat diet (HFD)-induced insulin-resistant mice and to investigate its mechanism based on inflammatory responses. Mice were fed a HFD to induce insulin resistance and then administered SB for nine weeks. Body weight, glucose, lipid, insulin, epididymal fat pad and liver weights, and histologic characteristics were evaluated to determine the effect on insulin resistance. In order to evaluate the effects on the inflammatory process, we analyzed the proportions of macrophages in liver and epididymal fat and measured inflammatory gene expression. Fasting and postprandial glucose, fasting insulin, HOMA-IR, triglycerides, and low density lipoprotein cholesterol levels were significantly decreased by SB administration. The epididymal fat and liver showed significant weight decreases and histological improvements. Total adipose tissue macrophages (ATMs) decreased (27.71 ± 3.47% vs. 45.26 ± 7.26%, p < 0.05), M2 ATMs increased (47.02 ± 6.63% vs. 24.28 ± 8.00%, p < 0.05), and CD11b+ Kupffer cells decreased. The expression levels of tumor necrosis factor alpha and F4/80 in the liver were significantly decreased (12.03 ± 1.47% vs. 25.88 ± 4.57%, p < 0.05) compared to HFD group. These results suggest that SB improved insulin resistance through inhibition of macrophage-mediated inflammation.

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Deleting myeloid IL-10 receptor signalling attenuates atherosclerosis in LDLR-/- mice by altering intestinal cholesterol fluxes

Thrombosis and Haemostasis ◽

10.1160/th16-01-0043 ◽

2016 ◽

Vol 116 (09) ◽

pp. 565-577 ◽

Cited By ~ 6

Author(s):

Gemma Brufau ◽

Marion J. J. Gijbels ◽

Ine M. J. Wolfs ◽

Saskia van der Velden ◽

Chantal C. H. Pöttgens ◽

...

Keyword(s):

Inflammatory Responses ◽

Cholesterol Metabolism ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cholesterol Homeostasis ◽

Liver Cholesterol ◽

Specific Cell ◽

Low Density ◽

Atherosclerosis Development ◽

Deficient Mice

SummaryInflammatory responses and cholesterol homeostasis are interconnected in atherogenesis. Interleukin (IL)-10 is an important anti-inflammatory cytokine, known to suppress atherosclerosis development. However, the specific cell types responsible for the atheroprotective effects of IL-10 remain to be defined and knowledge on the actions of IL-10 in cholesterol homeostasis is scarce. Here we investigated the functional involvement of myeloid IL-10-mediated atheroprotection. To do so, bone marrow from IL-10 receptor 1 (IL-10R1) wild-type and myeloid IL-10R1-deficient mice was transplanted to lethally irradiated female LDLR-/- mice. Hereafter, mice were given a high cholesterol diet for 10 weeks after which atherosclerosis development and cholesterol metabolism were investigated. In vitro, myeloid IL-10R1 deficiency resulted in a pro-inflammatory macrophage phenotype. However, in vivo significantly reduced lesion size and severity was observed. This phenotype was associated with lower myeloid cell accumulation and more apoptosis in the lesions. Additionally, a profound reduction in plasma and liver cholesterol was observed upon myeloid IL-10R1 deficiency, which was reflected in plaque lipid content. This decreased hypercholesterolaemia was associated with lowered very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels, likely as a response to decreased intestinal cholesterol absorption. In addition, IL-10R1 deficient mice demonstrated substantially higher faecal sterol loss caused by increased non-biliary cholesterol efflux. The induction of this process was linked to impaired ACAT2-mediated esterification of liver and plasma cholesterol. Overall, myeloid cells do not contribute to IL-10-mediated atheroprotection. In addition, this study demonstrates a novel connection between IL-10-mediated inflammation and cholesterol homeostasis in atherosclerosis. These findings make us reconsider IL-10 as a beneficial influence on atherosclerosis.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Modulation of hepatic apolipoprotein B, 3-hydroxy-3-methylglutaryl-CoA reductase and low-density lipoprotein receptor mRNA and plasma lipoprotein concentrations by defined dietary fats. Comparison of trimyristin, tripalmitin, tristearin and triolein

Biochemical Journal ◽

10.1042/bj3110167 ◽

1995 ◽

Vol 311 (1) ◽

pp. 167-173 ◽

Cited By ~ 31

Author(s):

A J Bennett ◽

M A Billett ◽

A M Salter ◽

E H Mangiapane ◽

J S Bruce ◽

...

Keyword(s):

Fatty Acids ◽

Plasma Lipids ◽

Low Density Lipoprotein ◽

Lipoprotein Metabolism ◽

Density Lipoprotein ◽

Dietary Fats ◽

Low Density ◽

Mrna Levels ◽

Expression Of Genes ◽

Coa Reductase

Different dietary fatty acids exert specific effects on plasma lipids but the mechanism by which this occurs is unknown. Hamsters were fed on low-cholesterol diets containing triacylglycerols enriched in specific saturated fatty acids, and effects on plasma lipids and the expression of genes involved in hepatic lipoprotein metabolism were measured. Trimyristin and tripalmitin caused significant rises in low-density lipoprotein (LDL) cholesterol which were accompanied by significant reductions in hepatic LDL receptor mRNA levels. Tripalmitin also increased hepatic expression of the apolipoprotein B gene, implying an increased production of LDL via very-low-density lipoprotein (VLDL) and decreased removal of LDL in animals fed this fat. Hepatic levels of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA did not vary significantly between the groups. Compared with triolein, tristearin had little effect on hepatic gene expression or total plasma cholesterol. However, it caused a marked decrease in VLDL cholesterol and a rise in LDL cholesterol such that overall it appeared to be neutral. Lipid analysis suggested a rapid desaturation of much of the dietary stearate. The differential changes in plasma lipids and hepatic mRNA levels induced by specific dietary fats suggests a role for fatty acids or a metabolite thereof in the regulation of the expression of genes involved in lipoprotein metabolism.

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The Very Low Density Lipoprotein Receptor Attenuates House Dust Mite–Induced Airway Inflammation by Suppressing Dendritic Cell–Mediated Adaptive Immune Responses

The Journal of Immunology ◽

10.4049/jimmunol.1301234 ◽

2014 ◽

Vol 192 (10) ◽

pp. 4497-4509 ◽

Cited By ~ 4

Author(s):

Karin Fredriksson ◽

Amarjit Mishra ◽

Jonathan K. Lam ◽

Elizabeth M. Mushaben ◽

Rosemarie A. Cuento ◽

...

Keyword(s):

Immune Responses ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Lipoprotein Receptor ◽

Adaptive Immune Responses ◽

Adaptive Immune ◽

Dust Mite ◽

Density Lipoprotein Receptor

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Effects of elevated CO2 levels on lung immune response to organic dust and lipopolysaccaride

10.21203/rs.3.rs-150712/v1 ◽

2021 ◽

Author(s):

David Schneberger ◽

Upkardeep Singh Pandher ◽

Brooke Thompson ◽

Shelley Kirychuk

Keyword(s):

Immune Responses ◽

Inflammatory Responses ◽

Animal Feed ◽

Weighted Average ◽

Innate Immune ◽

Mrna Levels ◽

Innate Immune Responses ◽

Organic Dust ◽

Complex Environments ◽

Time Weighted Average

Abstract Workplaces with elevated organic dust levels such as animal feed barns also commonly have elevated levels of gasses, such as CO2. Workers exposed to such complex environments often experience respiratory effects that may be due to a combination of respirable factors. We examined the effects of CO2 at the ASHRAE recommended limit (1000 ppm) as well as the EPA 8hr time weighted average limit (5000 ppm) on lung innate immune responses in mice with exposure to inflammatory lipopolysaccharide and organic dust. Mice were nasally instilled with dust extracts or LPS and immediately put into chambers with a constant flow of room air (approx. 430 ppm CO2), 1000 ppm, or 5000 ppm CO2 enriched air. Organic dust exposures tended to show decreased inflammatory responses with 1000 ppm CO2 and increased responses at 5000 ppm CO2. Conversely, LPS with addition of CO2 as low as 1000 ppm tended to inhibit several inflammatory markers. In most cases saline treated animals showed few changes with CO2 exposure, though some changes in mRNA levels were present. This shows that CO2 as low as 1000 ppm CO2 was capable of altering innate immune responses to both LPS and organic dust extracts, but each response was altered in a different fashion.

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Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21218312 ◽

2020 ◽

Vol 21 (21) ◽

pp. 8312

Author(s):

Takashi Obama ◽

Hiroyuki Itabe

Keyword(s):

Cardiovascular Diseases ◽

Inflammatory Responses ◽

Foam Cell ◽

Vascular Endothelial Cells ◽

Low Density Lipoprotein ◽

Cell Formation ◽

Density Lipoprotein ◽

Oxidative Modification ◽

Foam Cell Formation ◽

Low Density

Neutrophil extracellular traps (NETs) significantly contribute to various pathophysiological conditions, including cardiovascular diseases. NET formation in the vasculature exhibits inflammatory and thrombogenic activities on the endothelium. NETs are induced by various stimulants such as exogenous damage-associated molecular patterns (DAMPs). Oxidatively modified low-density lipoprotein (oxLDL) has been physiologically defined as a subpopulation of LDL that comprises various oxidative modifications in the protein components and oxidized lipids, which could act as DAMPs. oxLDL has been recognized as a crucial initiator and accelerator of atherosclerosis through foam cell formation by macrophages; however, recent studies have demonstrated that oxLDL stimulates neutrophils to induce NET formation and enhance NET-mediated inflammatory responses in vascular endothelial cells, thereby suggesting that oxLDL may be involved in cardiovascular diseases through neutrophil activation. As NETs comprise myeloperoxidase and proteases, they have the potential to mediate oxidative modification of LDL. This review summarizes recent updates on the analysis of NETs, their implications for cardiovascular diseases, and prospects for a possible link between NET formation and oxidative modification of lipoproteins.

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Toll-Like Receptor 9 Modulates Immune Responses to Aspergillus fumigatus Conidia in Immunodeficient and Allergic Mice

Infection and Immunity ◽

10.1128/iai.00998-08 ◽

2008 ◽

Vol 77 (1) ◽

pp. 108-119 ◽

Cited By ~ 57

Author(s):

Hemanth Ramaprakash ◽

Toshihiro Ito ◽

Theodore J. Standiford ◽

Steven L. Kunkel ◽

Cory M. Hogaboam

Keyword(s):

Immune Responses ◽

Aspergillus Fumigatus ◽

Inflammatory Responses ◽

Fungal Growth ◽

Lower Airway ◽

Interleukin 17 ◽

Toll Like Receptor ◽

Wild Type ◽

Immunodeficient Mice

ABSTRACT The role of Toll-like receptor 9 (TLR9) in antifungal responses in the immunodeficient and allergic host is unclear. We investigated the role of TLR9 in murine models of invasive aspergillosis and fungal asthma. Neutrophil-depleted TLR9 wild-type (TLR9+/+) and TLR9-deficient (TLR9−/−) mice were challenged with resting or swollen Aspergillus fumigatus conidia and monitored for survival and lung inflammatory responses. The absence of TLR9 delayed, but did not prevent, mortality in immunodeficient mice challenged with resting or swollen conidia compared to TLR9+/+ mice. In a fungal asthma model, TLR9+/+ and TLR9−/− mice were sensitized to soluble A. fumigatus antigens and challenged with resting or swollen A. fumigatus conidia, and both groups of mice were analyzed prior to and at days 7, 14, and 28 after the conidium challenge. When challenged with resting conidia, TLR9−/− mice exhibited significantly lower airway hyper-responsiveness compared to the TLR9+/+ groups. In contrast, A. fumigatus-sensitized TLR9−/− mice exhibited pulmonary fungal growth at days 14 and 28 after challenge with swollen conidia, a finding never observed in their allergic wild-type counterparts. Increased fungal growth in allergic TLR9−/− mice correlated with markedly decreased dectin-1 expression in whole lung samples and isolated dendritic cell populations. Further, whole lung levels of interleukin-17 were lower in allergic TLR9−/− mice compared to similar TLR9+/+ mice. Together, these data suggest that TLR9 modulates pulmonary antifungal immune responses to swollen conidia, possibly through the regulation of dectin-1 expression.

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Endotoxin suppresses rat hepatic low-density lipoprotein receptor expression

Biochemical Journal ◽

10.1042/bj3130873 ◽

1996 ◽

Vol 313 (3) ◽

pp. 873-878 ◽

Cited By ~ 19

Author(s):

Wei LIAO ◽

Mats RUDLING ◽

Bo ANGELIN

Keyword(s):

Time Course ◽

Low Density Lipoprotein ◽

Ldl Receptor ◽

Density Lipoprotein ◽

Receptor Expression ◽

Plasma Lipoproteins ◽

Low Density ◽

Mrna Levels ◽

Dependent Manner ◽

Receptor Mrna

Endotoxin induces hyperlipidaemia in experimental animals. In the current study, we investigated whether endotoxin alters hepatic low-density lipoprotein (LDL) receptor expression in rats. Endotoxin treatment suppressed hepatic LDL receptor expression in a dose- and time-dependent manner. Eighteen hours after intraperitoneal injection of increasing amounts of endotoxin, LDL receptor and its mRNA levels were determined by ligand blot and solution hybridization respectively. LDL receptor expression was inhibited by about 70% at a dose of 500 μg/100 g body weight. However, LDL receptor mRNA levels were markedly increased in all endotoxin-treated groups at this time point (by 83–136%; P < 0.001). Time-course experiments showed that LDL receptor expression was already reduced by 48% 4 h after endotoxin injection and was maximally reduced (by 63–65%) between 8 and 18 h. Changes in hepatic LDL receptor mRNA showed a different pattern. By 4 h after endotoxin injection, LDL receptor mRNA had decreased by 78% (P < 0.001). However, by 8 h after endotoxin injection, LDL receptor mRNA had returned to levels similar to controls, and 18 and 24 h after endotoxin injection, they were increased by about 60% (P < 0.05). Separation of plasma lipoproteins by FPLC demonstrated that endotoxin-induced changes in plasma triacylglycerols and cholesterol were due to accumulation of plasma apolipoprotein B-containing lipoproteins among very-low-density lipoprotein, intermediate-density lipoprotein and LDL. It is concluded that endotoxin suppresses hepatic LDL receptor expression in vivo in rats.

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HIV-1 Tat Regulates Occludin and AβTransfer Receptor Expression in Brain Endothelial Cells via Rho/ROCK Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/4196572 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 10

Author(s):

Yanlan Chen ◽

Wen Huang ◽

Wenlin Jiang ◽

Xianghong Wu ◽

Biao Ye ◽

...

Keyword(s):

Endothelial Cells ◽

Signaling Pathway ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Receptor Expression ◽

Immunofluorescent Staining ◽

Mrna Levels ◽

Protein Levels ◽

Density Lipoprotein Receptor ◽

Hiv 1

HIV-1 transactivator protein (Tat) has been shown to play an important role in HIV-associated neurocognitive disorders. The aim of the present study was to evaluate the relationship between occludin and amyloid-beta (Aβ) transfer receptors in human cerebral microvascular endothelial cells (hCMEC/D3) in the context of HIV-1-related pathology. The protein expressions of occludin, receptor for advanced glycation end products (RAGE), and low-density lipoprotein receptor-related protein 1 (LRP1) in hCMEC/D3 cells were examined using western blotting and immunofluorescent staining. The mRNA levels of occludin, RAGE, and LRP1 were measured using quantitative real-time polymerase chain reaction. HIV-1 Tat at 1 µg/mL and the Rho inhibitor hydroxyfasudil (HF) at 30 µmol/L, with 24 h exposure, had no significant effect on hCMEC/D3 cell viability. Treatment with HIV-1 Tat protein decreased mRNA and protein levels of occludin and LRP1 and upregulated the expression of RAGE; however, these effects were attenuated by HF. These data suggest that the Rho/ROCK signaling pathway is involved in HIV-1 Tat-mediated changes in occludin, RAGE, and LRP1 in hCMEC/D3 cells. HF may have a beneficial influence by protecting the integrity of the blood-brain barrier and the expression of Aβtransfer receptors.

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