scholarly journals Differences in HBV Replication, APOBEC3 Family Expression, and Inflammatory Cytokine Levels Between Wild-Type HBV and Pre-core (G1896A) or Basal Core Promoter (A1762T/G1764A) Mutants

2020 ◽  
Vol 11 ◽  
Author(s):  
Keith C. K. Lau ◽  
Shivali S. Joshi ◽  
Douglas J. Mahoney ◽  
Andrew L. Mason ◽  
Guido van Marle ◽  
...  
Keyword(s):  
Inflammatory Cytokine ◽  
Core Promoter ◽  
Basal Core Promoter ◽  
Wild Type ◽  
Hbv Replication ◽  
Cytokine Levels ◽  
Apobec3 Family

scholarly journals The effect of basal core promoter and pre-core mutations on HBV replication and persistence in mice

2020 ◽  
Author(s):  
Yi Chen ◽  
Zhiwei Xu ◽  
Yanli Zeng ◽  
Junping Liu ◽  
Yongjun Tian ◽  
...  
Keyword(s):  
Core Promoter ◽  
Infectious Clone ◽  
Site Directed Mutagenesis ◽  
Basal Core Promoter ◽  
Wild Type ◽  
Partial Loss ◽  
Ctl Response ◽  
Hbv Replication ◽  
Per Se

AbstractThe appearance of the BCP or Pre-C mutations, which reduce or abolish HBeAg production, could increase HBV replication. The remove of the HBeAg often lead to a vigorous immune response, which has an important role in HBV related fulminant outcome. In this study, BCP mutations and Pre-C mutations were separately introduced by site-directed mutagenesis in the same genetic background of an HBV infectious clone, to determine the effect of these mutations per se on replication. BCP and Pre-C mutations increased HBV replication both in vitro and in vivo. HBV could persist in mice injected with wild type HBV infectious clone for about 7 weeks. However, HBV could persist about 5 weeks in mice injected with BCP HBV infectious clone, and 3 weeks only in mice injected with Pre-C HBV infectious clone. HBV related CD8+ CTL response in BCP HBV infectious clone injected mice only slightly increased, but significantly increased in Pre-C HBV infectious clone injected mice compared with that in wild type HBV infectious clone injected mice. The population of Tregs significantly increased in liver but not in spleen of mice injected with Pre-C HBV infectious clone. In summary, we demonstrate that HBeAg plays an important role in suppressing the CTL response, which is related with increasing the frequency of Tregs in mouse. Lack of HBeAg expression leads to the partial loss of immune tolerance.

scholarly journals Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lidan Liu ◽  
Chaim Z. Aron ◽  
Cullen M. Grable ◽  
Adrian Robles ◽  
Xiangli Liu ◽  
...  
Keyword(s):  
Proinflammatory Cytokine ◽  
Inflammatory Cytokine ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Mrna Levels ◽  
Wild Type ◽  
Cytokine Mrna ◽  
Protein Levels ◽  
Cytokine Levels

AbstractLevels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.

Precore/Core Promoter Mutant Hepatitis B Virus Produces More Severe Histologic Liver Disease than Wild Type Hepatitis B Virus

2007 ◽  
Vol 1 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Mamun-Al-Mahtab ◽  
Salimur Rahman ◽  
Mobin Khan ◽  
Ayub Mamun ◽  
Kamal
Keyword(s):  
Liver Disease ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Core Promoter ◽  
Wild Type ◽  
B Virus ◽  
Promoter Mutant

THE EFFECT OF SUBACUTE INTOXICATION WITH ETHYLENE CHLOROHYDRIN ON IMMUNE RESPONSES, TH1 AND TH2 LYMPHOCYTE FUNCTION AND CYTOKINE LEVELS IN RATS BLOOD

2017 ◽  
pp. 27-30
Author(s):  
P. F. Zabrodskii ◽  
V. V. Maslyakov ◽  
M. S. Gromov
Keyword(s):  
Immune Responses ◽  
Inflammatory Cytokine ◽  
Albino Rats ◽  
Lymphocyte Function ◽  
Ethylene Chlorohydrin ◽  
Immunoregulatory Cytokines ◽  
Cytokine Levels ◽  
Th1 And Th2 Lymphocytes ◽  
Cellular Immune ◽  
Th1 And Th2

In experiments on outbred albino rats, it was established that subacute intoxication with ethylene chlorohydrin (0.2 LD50 daily for 4 days) causes a decrease in Th1 and Th2 lymphocytes function to the same extent, diminishes parameters of humoral and cellular immune responses and the content of immunoregulatory cytokines IFN- , IL-2, IL-4 in blood, increases concentrations of pro-inflammatory cytokine IL-6 and anti-inflammatory cytokine IL-10.

scholarly journals Role and Regulation of Adipokines during Zymosan-Induced Peritoneal Inflammation in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4080-4085 ◽  
Author(s):  
Maria Pini ◽  
Melissa E. Gove ◽  
Joseph A. Sennello ◽  
Jantine W. P. M. van Baal ◽  
Lawrence Chan ◽  
...  
Keyword(s):  
Inflammatory Infiltrate ◽  
Peritoneal Lavage ◽  
Lavage Fluid ◽  
Wild Type ◽  
Cellular Infiltrate ◽  
Peritoneal Lavage Fluid ◽  
Peritoneal Inflammation ◽  
Leptin Deficiency ◽  
Cytokine Levels

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNFα, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNFα, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.

scholarly journals A32 EMPAGLIFOZIN IMPROVES GASTROINTESTINAL INFLAMMATION IN A MOUSE MODEL OF COLITIS

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 213-215
Author(s):  
K Madsen ◽  
H Dang ◽  
N Hotte ◽  
V Mocanu ◽  
M Ferdaoussi ◽  
...  
Keyword(s):  
Animal Model ◽  
Sglt2 Inhibitor ◽  
Direct Effects ◽  
Lipocalin 2 ◽  
Wild Type ◽  
Gut Inflammation ◽  
Beneficial Effects ◽  
Histological Score ◽  
Cytokine Levels ◽  
Gastrointestinal Inflammation

Abstract Background Empagliflozin (EMPA) is a highly selective sodium glucose cotransporter-2 (SGLT2) inhibitor and is increasingly being utilized as an antihyperglycemic agent in the management of type 2 diabetes. Interestingly, it has been demonstrated in human trials that EMPA treatment exerts potent cardioprotective effects by reducing cardiac inflammation independently of glycemic control. Further, EMPA has also been shown to suppress LPS-induced renal and systemic inflammation in an animal model. Based on these findings, we hypothesized that EMPA treatment may also be effective in reducing gut inflammation. Aims The aim of this study was to examine the effects of treatment with EMPA on gastrointestinal inflammation in an animal model of inflammatory bowel disease and to determine mechanistic insights regarding its direct effects on gut cytokine secretion. Methods Adult male and female IL-10-/- mice with established colitis were treated with a daily gavage of EMPA (10mg/kg; n=10) or vehicle (n=10) for 14 days. Disease activity was assessed by measurement of mouse weight, colonic weight and length, histological score, cytokine levels in colonic homogenate and lipocalin-2 levels in stool. To examine for possible direct effects of EMPA, colonic explants from wild-type (n=8) and IL-10-/- (n=8) mice were incubated with increasing doses of EMPA (0.1–5 µM) ± LPS (10µg/ml) for 2 hours and tissue levels of IL-1β and TNFα protein measured by ELISA. Results After 14 days EMPA treated IL-10-/- mice had a significant improvement in colonic inflammation as evidenced by decreased colonic weight to length ratio (p=0.019), decreased fecal lipocalin-2 (p=0.03), as well as decreased enterocyte injury (p=0.01), decreased lamina propria neutrophils (p=0.01) and decreased total histological score (p=0.006). EMPA treated mice also maintained their weight over the 14 days while untreated mice continued to lose weight (p=0.04). There were no significant differences in colonic homogenate levels of TNFα, IL-1β, or IL-6 or in blood glucose levels between EMPA-treated mice and controls. In addition, EMPA did not suppress levels of basal or LPS-induced TNFα and IL-1β in colonic explants from either wild-type or IL-10-/- mice suggesting that the beneficial effects in IL-10-/- mice were not due to direct effects of EMPA on colonic TNFα or IL-1β cytokine levels. Conclusions EMPA treatment dramatically improved histologic and fecal inflammatory markers and maintained body weight in adult IL-10-/- mice with established colitis. These findings suggest further investigations into the effects of EMPA in treating gut inflammation are warranted. Funding Agencies CAG, CIHR

scholarly journals Acetylcholine-producing T cells augment innate immune-driven colitis but are redundant in T cell-driven colitis

2019 ◽  
Vol 317 (5) ◽  
pp. G557-G568 ◽  
Author(s):  
Rose A. Willemze ◽  
David J. Brinkman ◽  
Olaf Welting ◽  
Patricia H. P. van Hamersveld ◽  
Caroline Verseijden ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Inflammatory Cytokine ◽  
Dextran Sulfate ◽  
Dextran Sulfate Sodium ◽  
Innate Immune ◽  
Cytokine Levels ◽  
Colitis Model

Clinical trials suggest that vagus nerve stimulation presents an alternative approach to classical immune suppression in Crohn's disease. T cells capable of producing acetylcholine (ChAT+ T cells) in the spleen are essential mediators of the anti-inflammatory effect of vagus nerve stimulation. Besides the spleen, ChAT+ T cells are found abundantly in Peyer’s patches of the small intestine. However, the role of ChAT+ T cells in colitis pathogenesis is unknown. Here, we made use of CD4creChATfl/fl mice (CD4ChAT−/− mice) lacking ChAT expression specifically in CD4+ T cells. Littermates (ChATfl/fl mice) served as controls. In acute dextran sulfate sodium (DSS)-induced colitis (7 days of 2% DSS in drinking water), CD4ChAT−/− mice showed attenuated colitis and lower intestinal inflammatory cytokine levels compared with ChATfl/fl mice. In contrast, in a resolution model of DSS-induced colitis (5 days of 2% DSS followed by 7 days without DSS), CD4ChAT−/− mice demonstrated a worsened colitis recovery and augmented colonic histological inflammation scores and inflammatory cytokine levels as compared with ChATfl/fl mice. In a transfer colitis model using CD4+CD45RBhigh T cells, T cells from CD4ChAT−/− mice induced a similar level of colitis compared with ChATfl/fl T cells. Together, our results indicate that ChAT+ T cells aggravate the acute innate immune response upon mucosal barrier disruption in an acute DSS-induced colitis model, whereas they are supporting the later resolution process of this innate immune-driven colitis. Surprisingly, ChAT expression in T cells seems redundant in the context of T cell-driven colitis. NEW & NOTEWORTHY By using different mouse models of experimental colitis, we provide evidence that in dextran sulfate sodium-induced colitis, ChAT+ T cells capable of producing acetylcholine worsen the acute immune response, whereas they support the later healing phase of this innate immune-driven colitis.

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