scholarly journals Inflammatory Determinants of Differential Tuberculosis Risk in Pre-Adolescent Children and Young Adults

2021 ◽  
Vol 12 ◽  
Author(s):  
Richard Baguma ◽  
Stanley Kimbung Mbandi ◽  
Miguel J. Rodo ◽  
Mzwandile Erasmus ◽  
Jonathan Day ◽  
...  
Keyword(s):  
Young Adults ◽  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Very Young Children ◽  
Risk Of Progression ◽  
Children And Young Adults ◽  
Bead Arrays ◽  
Tuberculosis Risk ◽  
Stimulation Of

The risk of progression from Mycobacterium tuberculosis (M.tb) infection to active tuberculosis (TB) disease varies markedly with age. TB disease is significantly less likely in pre-adolescent children above 4 years of age than in very young children or post-pubescent adolescents and young adults. We hypothesized that pro-inflammatory responses to M.tb in pre-adolescent children are either less pronounced or more regulated, than in young adults. Inflammatory and antimicrobial mediators, measured by microfluidic RT-qPCR and protein bead arrays, or by analyzing published microarray data from TB patients and controls, were compared in pre-adolescent children and adults. Multivariate analysis revealed that M.tb-uninfected 8-year-old children had lower levels of myeloid-associated pro-inflammatory mediators than uninfected 18-year-old young adults. Relative to uninfected children, those with M.tb-infection had higher levels of similar myeloid inflammatory responses. These inflammatory mediators were also expressed after in vitro stimulation of whole blood from uninfected children with live M.tb. Our findings suggest that myeloid inflammation is intrinsically lower in pre-pubescent children than in young adults. The lower or more regulated pro-inflammatory responses may play a role in the lower risk of TB disease in this age group.

Cancer Risk in Children and Young Adults Conceived by In Vitro Fertilization

PEDIATRICS ◽  
2010 ◽  
Vol 126 (2) ◽  
pp. 270-276 ◽  
Author(s):  
B. Kallen ◽  
O. Finnstrom ◽  
A. Lindam ◽  
E. Nilsson ◽  
K.-G. Nygren ◽  
...  
Keyword(s):  
Young Adults ◽  
In Vitro Fertilization ◽  
Cancer Risk ◽  
Vitro Fertilization ◽  
Children And Young Adults

scholarly journals A200 HUMANIZED CELIAC-PRONE EPITHELIUM IN VITRO EXPRESS MHC-II AND CO-STIMULATORY MOLECULES NECESSARY FOR GLUTEN PEPTIDE PRESENTATION

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 73-74
Author(s):  
S Rahmani ◽  
H J Galipeau ◽  
H Su ◽  
F G Chirdo ◽  
T F Didar ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Antigen Presentation ◽  
Mhc Class Ii ◽  
Inflammatory Responses ◽  
Mhc Ii ◽  
Gluten Peptide ◽  
Peptide Presentation ◽  
Stimulation Of

Abstract Background The role intestinal epithelial cells (IECs) play in the breakdown of tolerance to gluten at an early stage in celiac disease (CeD) is unclear. Epithelial stress is a feature of CeD, and although the triggers are largely unknown, it is accompanied by expression of several markers that could be involved in initiation of inflammatory responses. IECs have been shown to express MHC class II (MHC-II) molecules and participate in antigen presentation in several models. Whether IECs can participate in gluten peptide presentation, the major environmental trigger in celiac disease, is unknown. To study this, a model expressing human MHC-II, HLA DQ8 or HLA-DQ2, would be required. Aims To develop organoid monolayers from transgenic mice expressing human celiac risk genes: HLA-DQ8 and -DQ2. To investigate conditions leading to the induction of epithelial MHC-II and its main co-stimulatory molecules, CD80, CD86 and CD40, that could enable early gluten peptide presentation. Methods In order to show pathophysiological significance of the model, we used two approaches, either induction of inflammation in vivo through gluten sensitization, or direct stimulation of the monolayers using pro-inflammatory cytokines relevant in CeD, such as IFNγ. Mice were sensitized with Pepsin-Trypsin digested gliadin and cholera toxin (CT) once a week for 3 weeks, followed by a challenge phase in which they only received gliadin. Control mice received CT only. We then developed organoid monolayers from the duodenum followed by stimulation with 10 ng/ml IFNγ. Finally, markers necessary for gluten peptide presentation, the expression of MHC-II and its co-stimulatory molecules, were evaluated using flow cytometry. Results Both in vivo gluten sensitization and in vitro stimulation of the organoid derived monolayer with IFNγ induced a proinflammatory response, that independently primed the epithelium to express MHC-II molecules (p =0.02 and <0.0001, respectively). When in vivo sensitization and in vitro IFNγ stimulation were combined, epithelial MHC-II expression was further upregulated (p <0.0001). Lastly, only the combination of gluten sensitization and in vitro IFNγ induced expression of MHC-II co-stimulatory molecules, which are necessary for antigen presentation. Conclusions Our findings support that gluten induced-inflammation in vivo as well as independent stimuli that release IFNγ enhance the capacity of the IECs to express MHC-II molecules. However, co-stimulatory molecules are only expressed by the epithelium when both gluten tolerance is broken by in vivo sensitization and the organoid monolayers is further exposed to IFNγ. The results support the hypothesis that the epithelium participates in gluten peptide presentation and that this pathway is stimulated by both gluten-dependent and independent inflammation. Funding Agencies CIHRSupported by CIHR and a Farncombe Family Grant to EFV and TFD.

Stimulation of inflammatory responses in vitro and in vivo by lipophilic HMG-CoA reductase inhibitors

2001 ◽  
Vol 1 (1) ◽  
pp. 105-118 ◽  
Author(s):  
Peter A Kiener ◽  
Patricia M Davis ◽  
Judy L Murray ◽  
Sonia Youssef ◽  
Bruce M Rankin ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase ◽  
Stimulation Of

scholarly journals Inflammatory Responses of Bovine Polymorphonuclear Neutrophils Induced by Staphylococcal Enterotoxin C via Stimulation of Mononuclear Cells

2003 ◽  
Vol 10 (6) ◽  
pp. 1011-1018 ◽  
Author(s):  
Toshinobu Kuroishi ◽  
Ken-ichi Komine ◽  
Ken-ichi Asai ◽  
Jin Kobayashi ◽  
Kouichi Watanabe ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Mammary Glands ◽  
Staphylococcal Enterotoxin ◽  
Polymorphonuclear Neutrophils ◽  
Histopathological Analysis ◽  
Peripheral Blood Mononuclear ◽  
Long Time ◽  
Stimulation Of

ABSTRACT To elucidate the pathological roles of staphylococcal enterotoxin C (SEC) in bovine staphylococcal mastitis, a histopathological analysis of SEC-inoculated mammary glands was performed. SEC-inoculated mammary glands exhibited interstitial inflammation, and the leukocytes that migrated into the gland were predominantly polymorphonuclear neutrophils (PMN). In the gland cistern tissues dissected from SEC-inoculated mammary glands, epithelial cellular degeneration was observed. We also investigated the physiological effects of SEC on PMN in vitro. PMN migration was induced by culture supernatant of SEC-stimulated peripheral blood mononuclear cells (S-PBMC sup) but not by that of nonstimulated PBMC (N-PBMC sup). The concentration of interleukin-8 was significantly (P < 0.05) higher in S-PBMC sup than N-PBMC sup, and a significantly (P < 0.05) higher mRNA expression of growth-regulated oncogenes was detected in SEC-stimulated PBMC than in nonstimulated PBMC. Milk PMN collected from SEC-inoculated mammary glands produced more than 2 times the amount of superoxide at 1 day postinoculation (dpi) than at 0 dpi in the presence of phorbol 12-myristate 13-acetate (PMA). PMN cultured with S-PBMC sup for 24 h also produced significantly (P < 0.05) larger amounts of superoxide than those cultured with N-PBMC sup in the presence of PMA. Moreover, S-PBMC sup induced the long-time survival of PMN. These results indicate that SEC induces the activation of PMN via the stimulation of mononuclear cells.

scholarly journals Evaluation of Fat Accumulation and Adipokine Production during the Long-Term Adipogenic Differentiation of Porcine Intramuscular Preadipocytes and Study of the Influence of Immunobiotics

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1715
Author(s):  
Asuka Tada ◽  
AKM Humayun Kober ◽  
Md. Aminul Islam ◽  
Manami Igata ◽  
Michihiro Takagi ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Adipogenic Differentiation ◽  
Tissue Mass ◽  
Fat Accumulation ◽  
Effector Cells ◽  
Tnf Α ◽  
Increasing Trend ◽  
Stimulation Of

The degree of fat accumulation and adipokine production are two major indicators of obesity that are correlated with increased adipose tissue mass and chronic inflammatory responses. Adipocytes have been considered effector cells for the inflammatory responses due to their capacity to express Toll-like receptors (TLRs). In this study, we evaluated the degree of fat accumulation and adipokine production in porcine intramuscular preadipocyte (PIP) cells maintained for in vitro differentiation over a long period without or with stimulation of either TNF-α or TLR2-, TLR3-, or TLR4-ligands. The cytosolic fat accumulation was measured by liquid chromatography and the expression of adipokines (CCL2, IL-6, IL-8 and IL-10) were quantified by RT-qPCR and ELISA at several time points (0 to 20 days) of PIP cells differentiation. Long-term adipogenic differentiation (LTAD) induced a progressive fat accumulation in the adipocytes over time. Activation of TLR3 and TLR4 resulted in an increased rate of fat accumulation into the adipocytes over the LTAD. The production of CCL2, IL-8 and IL-6 were significantly increased in unstimulated adipocytes during the LTAD, while IL-10 expression remained stable over the studied period. An increasing trend of adiponectin and leptin production was also observed during the LTAD. On the other hand, the stimulation of adipocytes with TLRs agonists or TNF-α resulted in an increasing trend of CCL2, IL-6 and IL-8 production while IL-10 remained stable in all four treatments during the LTAD. We also examined the influences of several immunoregulatory probiotic strains (immunobiotics) on the modulation of the fat accumulation and adipokine production using supernatants of immunobiotic-treated intestinal immune cells and the LTAD of PIP cells. Immunobiotics have shown a strain-specific ability to modulate the fat accumulation and adipokine production, and differentiation of adipocytes. Here, we expanded the utility and potential application of our in vitro PIP cells model by evaluating an LTAD period (20 days) in order to elucidate further insights of chronic inflammatory pathobiology of adipocytes associated with obesity as well as to explore the prospects of immunomodulatory intervention for obesity such as immunobiotics.

scholarly journals Anti-Inflammatory Effects ofSiegesbeckia orientalisEthanol Extract inIn VitroandIn VivoModels

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yong-Han Hong ◽  
Li-Wen Weng ◽  
Chi-Chang Chang ◽  
Hsia-Fen Hsu ◽  
Chao-Ping Wang ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Animal Experiments ◽  
Ethanol Extract ◽  
Raw264.7 Cells ◽  
Control Group ◽  
Dependent Manner ◽  
Anti Inflammatory

This study aims to investigate the anti-inflammatory responses and mechanisms ofSiegesbeckia orientalisethanol extract (SOE). In cell culture experiments, RAW264.7 cells were pretreated with SOE and stimulated with lipopolysaccharide (LPS) for inflammatory mediators assay. In animal experiments, mice were tube-fed with SOE for 1 week, and s.c. injected withλ-carrageenan or i.p. injected with LPS to simulate inflammation. The degree of paw edema was assessed, and cytokine profile in sera and mouse survival were recorded. Data showed that SOE significantly reduced NO, IL-6, and TNF-α production in LPS-stimulated RAW264.7 cells.In vivostudies demonstrated that mice supplemented with 32 mg SOE/kg BW/day significantly lowered sera IL-6 level and resulted a higher survival rate compared to the control group (P=0.019). Furthermore, SOE inhibited LPS-induced NF-κB activation by blocking the degradation of IκB-α. The SOE also reduced significantly the phosphorylation of ERK1/2, p38, and JNK in a dose-dependent manner. In summary, thein vitroandin vivoevidence indicate that SOE can attenuate acute inflammation by inhibiting inflammatory mediators via suppression of MAPKs- and NF-κB-dependent pathways.

302. Characterisation of lipopolysaccharide (LPS) receptor expression and the inflammatory response of the rat testis

2005 ◽  
Vol 17 (9) ◽  
pp. 128
Author(s):  
W. Winnall ◽  
J. Muir ◽  
P. Hutchinson ◽  
M. Hedger
Keyword(s):  
Mrna Expression ◽  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Inflammatory Responses ◽  
Receptor Expression ◽  
Spermatogenic Cells ◽  
Testicular Macrophages

Inflammation in the testis is disastrous for the developing spermatogenic cells, leading to temporary and sometimes permanent sterility. The majority of testicular macrophages display a unique protective phenotype whereby production of some key inflammatory mediators, specifically interleukin-1β (IL-1β), tumour necrosis factor-α (TNFα) and NO, in response to stimulation with LPS is relatively poor. Leydig cells and Sertoli cells also respond to high doses of LPS, producing the inflammatory cytokines, particularly IL-1α and IL-6. Although these data suggest that the LPS receptor (toll-like receptor 4, TLR4) and its associated binding proteins, CD14 and MD2, are expressed on several testicular cell types, expression of these proteins in the testis has not been described previously. Using real-time PCR and Western blotting, we established that TLR4, CD14 and MD2 are all expressed by testicular macrophages, Leydig cells, Sertoli cells, spermatocytes and round spermatids. Unexpectedly, the spermatogenic cells displayed the highest level of TLR4 surface expression as determined by flow cytometry. There was no response of the spermatogenic cells to LPS stimulation in vitro, at least in terms of mRNA expression for the inflammatory cytokines, IL-1α, IL-1β, TNFα, IL-6, activin A and the chemoattractants, CXCL-1 and CXCL-2. Although production of several cytokines was relatively diminished, testicular macrophages responded to LPS with a significant increase in mRNA expression for all of these inflammatory regulators. These data indicate that the protective phenotype of the testicular macrophages is not due to insensitivity to LPS or absence of the receptor, but may involve downstream regulation of specific inflammatory responses. The data also suggest that spermatogenic cells are capable of responding to TLR4 ligands, although not by producing inflammatory mediators. The actual function of the LPS receptor on the spermatogenic cells remains to be discovered.

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