scholarly journals The migration ofAscaris suumlarvae, and the associated pulmonary inflammatory response in susceptible C57BL/6j and resistant CBA/Ca mice

Parasitology ◽  
2007 ◽  
Vol 134 (9) ◽  
pp. 1301-1314 ◽  
Author(s):  
R. Lewis ◽  
J. M. Behnke ◽  
J. P. Cassidy ◽  
P. Stafford ◽  
N. Murray ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Lavage Fluid ◽  
Intestinal Wall ◽  
Post Inoculation ◽  
Larval Stages ◽  
Stage Of Development ◽  
Pulmonary Inflammatory Response ◽  
The Difference ◽  
Susceptibility And Resistance

SUMMARYAscariasis is an important infection in humans (Ascaris lumbricoides) and pigs (Ascaris suum) and individuals appear to be predisposed to either heavy or light worm burdens. These extremes of susceptibility and resistance are represented in a mouse model by 2 strains of mice, CBA mice showing high resistance to infection and C57BL/6 which are highly susceptible, as reflected in worm burdens in the lungs 6–7 days after infection. In an attempt to identify the point at which the difference between these 2 strains is first manifested, we quantified worm burdens at key stages during infection leading up to the pulmonary stage of development. Thus mice were inoculated with fully embryonatedA. suumeggs and larval burdens were enumerated in the large intestine and rectum, liver and lungs of the 2 strains at 6 h post-inoculation (p.i.) and on each of days 1–8 p.i. inclusively. A higher percentage of the total inoculum was recovered from the intestine/rectum of C57BL/6j mice in contrast to CBA/Ca mice at 6 h p.i. Larvae were recovered from the intestinal contents and also whilst actively migrating through the large intestinal wall. The number of larvae recovered was significantly reduced in CBA/Ca mice in contrast to C57BL/6j mice between the phase of migration from the liver and arrival in the lungs. The combined results of the inoculation of mice with corticosteroids and the examination of the change in profile and number of leukocytes present in bronchoalveolar lavage fluid suggested that the pulmonary inflammatory immune response was not prominently involved in primary protection of mice toA. suuminfection in the latter days of infection in the lungs. The susceptible C57BL/6j mice produced a BAL response almost twice as intense as that of resistant CBA/Ca mice with stronger neutrophil, lymphocyte and eosinophil but not macrophage components, suggesting that the difference in worm burdens between the strains was generated earlier in the course of infection. These results were further corroborated by a histological examination of the lung tissues which showed that the passage of the larval stages ofA. suumthrough the mouse lungs was associated with a marked inflammatory response in both strains. Again, C57BL/6j mice exhibited increased inflammation relative to CBA/Ca mice. Hence some hepatic/post-hepatic factor that varies between the 2 strains, but exerts its effect before the lung phase plays a critical role in determining the success of larvae through the host tissues. The possible sites of this host defence are reviewed.

scholarly journals Reduction by Cefodizime of the Pulmonary Inflammatory Response Induced by Heat-Killed Streptococcus pneumoniae in Mice

1998 ◽  
Vol 42 (10) ◽  
pp. 2527-2533 ◽  
Author(s):  
Yves Bergeron ◽  
Nathalie Ouellet ◽  
Anne-Marie Deslauriers ◽  
Marie Simard ◽  
Martin Olivier ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Inflammatory Response ◽  
Pneumococcal Infection ◽  
Fluorescein Isothiocyanate ◽  
Lavage Fluid ◽  
Necrosis Factor Alpha ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Pulmonary Inflammatory Response ◽  
Tract Infections

ABSTRACT It has recently become apparent that overwhelming inflammatory reactions contribute to the high mortality rate associated with pneumococcal infection in immunocompetent hosts. Cefodizime (CEF) is an antibiotic that seems to be endowed with immunomodulating properties. To investigate the influence of CEF on the pulmonary inflammatory response induced by Streptococcus pneumoniae, we infected mice with repeated intranasal inoculations of 107 CFU of heat-killed fluorescein isothiocyanate-labeled bacteria, which are insensitive to the killing properties of the drug. CEF downregulated but did not abolish the strong polymorphonuclear leukocyte (PMN) recruitment induced by S. pneumoniae. PMN recruitment was not primarily mediated by leukotriene B4 in this model. The drug did not interfere with intrinsic mechanisms of phagocytosis by PMNs and alveolar macrophages. CEF totally abrogated the pneumococcus-induced tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion in bronchoalveolar lavage fluid. The drug also prevented IL-6 release in lung homogenates and partly inhibited TNF-α, but it did not interfere with IL-1α secretion in the lungs of infected mice. The fractional and selective downregulation of inflammatory cells and cytokines by CEF suggests cell-specific and intracellular specific mechanisms of interaction of the drug. The immunomodulatory properties of CEF may help restrain excessive inflammatory reactions, thus contributing to the reported good clinical efficacy of the drug against lower respiratory tract infections.

scholarly journals Role of Lysosomes in Silica-Induced Inflammasome Activation and Inflammation in Absence of MARCO

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Rupa Biswas ◽  
Raymond F. Hamilton ◽  
Andrij Holian
Keyword(s):  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Acid Sphingomyelinase ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
The Difference ◽  
Silica Treatment

MARCO is the predominant scavenger receptor for recognition and binding of silica particles by alveolar macrophages (AM). Previously, it was shown that mice null for MARCO have a greater inflammatory response to silica, but the mechanism was not described. The aim of this study was to determine the relationship between MARCO and NLRP3 inflammasome activity. Silica increased NLRP3 inflammasome activation and release of the proinflammatory cytokine, IL-1β, to a greater extent in MARCO−/−AM compared to wild type (WT) AM. Furthermore, in MARCO−/−AM there was greater cathepsin B release from phagolysosomes, Caspase-1 activation, and acid sphingomyelinase activity compared to WT AM, supporting the critical role played by lysosomal membrane permeabilization (LMP) in triggering silica-induced inflammation. The difference in sensitivity to LMP appears to be in cholesterol recycling since increasing cholesterol in AM by treatment with U18666A decreased silica-induced NLRP3 inflammasome activation, and cells lacking MARCO were less able to sequester cholesterol following silica treatment. Taken together, these results demonstrate that MARCO contributes to normal cholesterol uptake in macrophages; therefore, in the absence of MARCO, macrophages are more susceptible to a greater inflammatory response by particulates known to cause NLRP3 inflammasome activation and the effect is due to increased LMP.

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

scholarly journals RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA

2020 ◽  
pp. jbc.RA120.014894
Author(s):  
Ravi Kumar ◽  
Dipak Kumar Poria ◽  
Partho Sarothi Ray
Keyword(s):  
Inflammatory Response ◽  
Chronic Inflammation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Regulation Of Gene Expression ◽  
Mrna Translation ◽  
Suppressor Gene ◽  
Cooperative Action ◽  
Translation Repression

Post-transcriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a pro-inflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) HuR in response to LPS stimulation, but the role of other regulatory factors remain unknown. Here we report that the RBP Lupus antigen (La) interacts with the 3’UTR of PDCD4 mRNA and prevents miR-21-mediated translation repression. While LPS causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

scholarly journals Pulmonary inflammatory response from co-exposure to LPS and glyphosate

2021 ◽  
Vol 86 ◽  
pp. 103651
Author(s):  
Upkardeep Pandher ◽  
Shelley Kirychuk ◽  
David Schneberger ◽  
Brooke Thompson ◽  
Gurpreet Aulakh ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Pulmonary Inflammatory Response

scholarly journals Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Qiancheng Luo ◽  
Rui Liu ◽  
Kaili Qu ◽  
Guorong Liu ◽  
Min Hang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lavage Fluid ◽  
Surface Expression ◽  
Pulmonary Injury ◽  
Protective Mechanisms ◽  
Tnf Α ◽  
Anti Platelet Drug ◽  
G Protein Coupled ◽  
Very High ◽  
Masson Staining

Abstract Background Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. Methods In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. Results TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1β (p  < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001). Conclusion Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

The influence of dietary carbohydrates on experimental infection withTrichuris suisin pigs

Parasitology ◽  
2005 ◽  
Vol 132 (6) ◽  
pp. 857-865 ◽  
Author(s):  
L. E. THOMSEN ◽  
S. PETKEVIČIUS ◽  
K. E. BACH KNUDSEN ◽  
A. ROEPSTORFF
Keyword(s):  
Sugar Beet ◽  
Experimental Infection ◽  
Diet Group ◽  
The Other ◽  
Post Inoculation ◽  
Dietary Carbohydrates ◽  
Barley Flour ◽  
Faecal Egg Counts ◽  
The Difference ◽  
Fermentable Carbohydrates

Two experiments (Exps 1 and 2) were carried out to study the effect of dietary carbohydrates on the establishment ofTrichuris suisin pigs. Two experimental diets based on barley flour were used; Diet 1 was supplemented with non-fermentable carbohydrates from oat hull meal, while Diet 2 was supplemented with fermentable carbohydrates from sugar beet fibre and inulin. In Exp. 1, thirty-two pigs were allocated randomly into 4 groups. Two groups were fed Diet 1 and 2 groups were fed Diet 2. Pigs from one of each diet group were inoculated with 2000 infectiveT. suiseggs each and the other two groups were uninfected controls. All pigs were slaughtered 8 weeks post-inoculation (p.i.). In Exp. 2, twenty-four pigs were allocated randomly into 2 groups and fed Diet 1 or Diet 2, respectively. All the pigs were inoculated with 2000 infectiveT. suiseggs. Six pigs from each group were slaughtered 8 weeks p.i. and the remaining 6 pigs from each group were slaughtered 12 weeks p.i. Infections were followed by faecal egg counts and worm burdens were assessed at necropsy. Pigs fed Diet 2 had lower egg counts in both experiments; in Exp. 2 the difference was significant (P<0·05). No differences were found in worm burdens 8 weeks p.i. in both experiments, however, worms from pigs on Diet 2 were significantly shorter (P<0·0001). Pigs fed Diet 2 and slaughtered 12 weeks p.i. had significantly lower worm counts (P<0·01) compared to pigs fed Diet 1. The results indicate that fermentable carbohydrates do not affect the establishment ofT. suisin naïve pigs, but result in earlier expulsion and reduced growth of the established worms. Thus, diets with highly fermentable carbohydrates may be used in the control ofT. suis.

scholarly journals Seasonal occurrence of some larval stages of endoparasites in three cyprinids from the Nwanedi-Luphephe dams, the Limpopo River System, South Africa

2015 ◽  
Vol 52 (3) ◽  
pp. 229-235 ◽  
Author(s):  
E. M. Mbokane ◽  
J. Theron ◽  
W. J. Luus-Powell
Keyword(s):  
Developmental Stages ◽  
River System ◽  
Intestinal Wall ◽  
The Body ◽  
Seasonal Occurrence ◽  
Seasonal Fluctuations ◽  
Metazoan Parasites ◽  
Larval Stages ◽  
Parasite Communities ◽  
Third Stage

Abstract This study provides information on seasonal occurrence of developmental stages of endoparasites infecting three cyprinids in the Nwanedi-Luphephe dams, Limpopo River System. Labeobarbus marequensis (Smith, 1841), Barbus trimaculatus Peters, 1852 and Barbus radiatus Peters, 1853 were investigated seasonally from January 2008 to October 2008. The following larvae of metazoan parasites were collected: Diplostomum sp. from the eyes of L. marequensis and B. trimaculatus; Ornithodiplostomum sp. from the gills of B. trimaculatus; Posthodiplostomum sp. from muscle, skin and fins of B. trimaculatus and B. radiatus; third-stage Contracaecum larvae (L3) from the mesentery fats and on the liver lobes of L. marequensis and B. trimaculatus and gryporynchid cestode larvae from the outer intestinal wall of B. radiatus. All the flukes encountered were metacercariae. Diplostomum sp. and Contracaecum sp. dominated the parasite communities. Their prevalence exhibited seasonal fluctuations with maxima in summer. Factors likely to influence fish infection such as the body size of fish and their condition factors were also briefly considered in this study.

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