scholarly journals Environmental Factor-Mediated Transgenerational Inheritance of Igf2r Hypomethylation and Pulmonary Allergic Response via Targeting Dendritic Cells

2020 ◽  
Vol 11 ◽  
Author(s):  
Jau-Ling Suen ◽  
Tai-Ting Wu ◽  
Yue-Hyuan Li ◽  
Chin-Lai Lee ◽  
Fu-Chen Kuo ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Low Dose ◽  
Epigenetic Modification ◽  
Allergic Diseases ◽  
Underlying Mechanism ◽  
Allergic Response ◽  
Consequent Reduction ◽  
Ifn Γ ◽  
Ligand Stimulation ◽  
Ethylhexyl Phthalate

The developmental origin of allergic diseases has been suggested, but the molecular basis remains enigmatic. Exposure to environmental factors, such as di-(2-ethylhexyl) phthalate (DEHP; a common plasticizer), is suggested to be associated with increased childhood allergic asthma, but the causal relationship and its underlying mechanism remain unknown. This study explored the transgenerational mechanism of DEHP on allergic asthma and dendritic cell (DC) homeostasis through epigenetic modification. In a murine model, ancestral exposure of C57BL/6 mice to low-dose DEHP led to trans-generational promoter hypomethylation of the insulin-like growth factor 2 receptor (Igf2r), concomitant with enhanced Igf2r expression and increased apoptosis prominently in CD8α+ DCs upon ligand stimulation, with consequent reduction in their IL-12 secretion and subsequent T cell-derived IFN-γ, thereby promoting a default Th2-associated pulmonary allergic response. Increased apoptosis was also noted in circulating IGF2Rhigh human DCs. Further, in human placenta, the methylation level at the orthologous IGF2R promoter region was shown to be inversely correlated with the level of maternal DEHP intake. These results support the importance of ancestral phthalate exposure in conferring the trans-generational risk of allergic phenotypes, featuring hypo-methylation of the IGF2R gene and dysregulated DC homeostasis.

TLR7 ligand prevents allergen-induced airway hyperresponsiveness and eosinophilia in allergic asthma by a MYD88-dependent and MK2-independent pathway

2006 ◽  
Vol 290 (5) ◽  
pp. L987-L995 ◽  
Author(s):  
J. Moisan ◽  
P. Camateros ◽  
T. Thuraisingam ◽  
D. Marion ◽  
H. Koohsari ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Allergic Diseases ◽  
Bronchial Tree ◽  
Protective Effects ◽  
Toll Like Receptor ◽  
Asthma Model ◽  
Ifn Γ ◽  
Clinical Potential ◽  
Tlr7 Ligand ◽  
Inflammatory Effect

Asthma is one of the leading causes of childhood hospitalization, and its incidence is on the rise throughout the world. Currently, the standard treatment for asthma is the use of corticosteroids to try to suppress the inflammatory reaction taking place in the bronchial tree. Using a murine model of atopic allergic asthma employing a methacholine-hyperresponsive (A/J) as well as a hyporesponsive (C57BL/6) strain of mice sensitized and challenged with ovalbumin, we show that treatment with a synthetic Toll-like receptor 7 (TLR7) ligand (S-28463, a member of the imidazoquinoline family) prevents development of the asthmatic phenotype. Treatment with S-28463 resulted in a reduction of airway resistance and elastance following ovalbumin sensitization and challenge. This was accompanied by a dramatic reduction in infiltration of leukocytes, especially eosinophils, into the lungs of both C57BL/6 and A/J mice following OVA challenge. Treatment with S-28463 also abolished both the elevation in serum IgE level as well as the induction of IL-4, IL-5, and IL-13 by OVA challenge. The protective effects of S-28463 were also observed in MK2 knockout, but not MYD88 knockout, mice. We did not observe a switch in cytokine profile from TH2 to TH1, as both IL-12p70 and IFN-γ levels were reduced following S-28463 treatment. These results clearly demonstrate the anti-inflammatory effect of imidazoquinolines in an allergic asthma model as well as the clinical potential of TLR7 ligands in the treatment of allergic diseases.

Epigenetic modifications in acute lymphoblastic leukemia: From cellular mechanisms to therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi ◽  
Soheila Montazersaheb ◽  
Yasin Bagheri
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Histone Modification ◽  
Epigenetic Modification ◽  
Lymphoblastic Leukemia ◽  
Underlying Mechanism ◽  
Methylation Pattern ◽  
Epigenetic Alterations ◽  
Cellular Mechanisms ◽  
Novel Treatments

Background:: Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic altera-tions as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, be-yond available conventional therapy. Objective:: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and pro-gression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and mi-croRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel well-suited approaches against ALL. Conclusion:: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifica-tions, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

Polymicrobial Sepsis but Not Low-Dose Endotoxin Infusion Causes Decreased Splenocyte IL-2/IFN-γ Release While Increasing IL-4/IL-10 Production

1994 ◽  
Vol 56 (6) ◽  
pp. 579-585 ◽  
Author(s):  
Alfred Ayala ◽  
Zoe K. Deol ◽  
Donna L. Lehman ◽  
Crystal D. Herdon ◽  
Irshad H. Chaudry
Keyword(s):  
Low Dose ◽  
Polymicrobial Sepsis ◽  
Endotoxin Infusion ◽  
Ifn Γ

MyD88-Dependent Glucose Restriction and Itaconate Production Control Brucella Infection

2021 ◽  
Author(s):  
Carolyn A. Lacey ◽  
Bárbara Ponzilacqua-Silva ◽  
Catherine A. Chambers ◽  
Alexis S. Dadelahi ◽  
Jerod A. Skyberg
Keyword(s):  
Glucose Transporter ◽  
Production Control ◽  
Brucella Melitensis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ifn Γ ◽  
Glucose Restriction ◽  
Myd88 Signaling

Brucellosis is one of the most common global zoonoses and is caused by facultative intracellular bacteria of the genus Brucella . Numerous studies have found that MyD88 signaling contributes to protection against Brucella , however the underlying mechanism has not been entirely defined. Here we show that MyD88 signaling in hematopoietic cells contributes both to inflammation and to control of Brucella melitensis infection in vivo . While the protective role of MyD88 in Brucella infection has often been attributed to promotion of IFN-γ production, we found that MyD88 signaling restricts host colonization by B. melitensis even in the absence of IFN-γ. In vitro , we show that MyD88 promotes macrophage glycolysis in response to B. melitensis . Interestingly, a B. melitensis mutant lacking the glucose transporter, GluP, was more highly attenuated in MyD88 -/- than in WT mice, suggesting MyD88 deficiency results in an increased availability of glucose in vivo which Brucella can exploit via GluP. Metabolite profiling of macrophages identified several metabolites regulated by MyD88 in response to B. melitensis , including itaconate. Subsequently, we found that itaconate has antibacterial effects against Brucella and also regulates the production of pro-inflammatory cytokines in B. melitensis -infected macrophages. Mice lacking the ability to produce itaconate were also more susceptible to B. melitensis in vivo . Collectively, our findings indicate that MyD88-dependent changes in host metabolism contribute to control of Brucella infection.

scholarly journals Is suicidal ideation associated with allergic asthma and allergic rhinitis?

2018 ◽  
Vol 44 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Martín Bedolla-Barajas ◽  
Norma Angélica Pulido-Guillén ◽  
Bolívar Vivar-Aburto ◽  
Jaime Morales-Romero ◽  
José Raúl Ortiz-Peregrina ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Suicidal Ideation ◽  
Allergic Asthma ◽  
Allergic Diseases ◽  
Cross Sectional Study ◽  
University Hospital ◽  
Control Group ◽  
Healthy Controls ◽  
Cross Sectional ◽  
And Control

ABSTRACT Objective: To investigate whether there is an association between suicidal ideation (SI) and allergic diseases in adults. Methods: This was a comparative cross-sectional study involving individuals ranging from 20 to 50 years of age recruited from a university hospital in the city of Guadalajara, Mexico. We included patients with a confirmed diagnosis of allergic asthma, those with a confirmed diagnosis of allergic rhinitis, and healthy controls. All subjects completed the Beck Depression Inventory-II (BDI-II), which includes an item that evaluates the presence of suicidal thoughts or desires within the last two weeks, in order to identify SI. Results: The sample comprised 115 patients with allergic asthma, 111 patients with allergic rhinitis, and 96 healthy controls. The number of individuals identified with SI in the three groups were, respectively, 17 (14.8%), 13 (11.7%), and 8 (8.3%). Regarding the presence of SI, no statistically significant association was found in the allergic asthma group (OR = 1.98; 95% CI: 0.78-4.64; p = 0.154) or in the allergic rhinitis group (OR = 1.46; 95% CI: 0.58-3.68; p = 0.424) when they were compared with the control group. However, the presence of depression was associated with SI in the three groups: allergic asthma (OR = 12.36; 95% CI: 2.67-57.15; p = 0.001); allergic rhinitis (OR = 6.20; 95% CI: 1.66-23.14; p = 0.006); and control (OR = 21.0; 95% CI: 3.75-117.36; p < 0,001). Conclusions: In comparison with the control group, no association was found between SI and the groups with allergic diseases. In contrast, there was association between SI and depression in the three groups.

scholarly journals Interleukin 18 Acts on Memory T Helper Cells Type 1 to Induce Airway Inflammation and Hyperresponsiveness in a Naive Host Mouse

2004 ◽  
Vol 199 (4) ◽  
pp. 535-545 ◽  
Author(s):  
Takaaki Sugimoto ◽  
Yuriko Ishikawa ◽  
Tomohiro Yoshimoto ◽  
Nobuki Hayashi ◽  
Jiro Fujimoto ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Bronchial Asthma ◽  
Allergic Diseases ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Inflammatory Protein ◽  
Ifn Γ ◽  
Factor Α

Interleukin (IL)-18 was originally regarded to induce T helper cell (Th)1-related cytokines. In general, factors favoring interferon (IFN)-γ production are believed to abolish allergic diseases. Thus, we tested the role of IL-18 in regulation of bronchial asthma. To avoid a background response of host-derived T cells, we administered memory type Th1 or Th2 cells into unsensitized mice and examined their role in induction of bronchial asthma. Administration of antigen (Ag) induced both airway inflammation and airway hyperresponsiveness (AHR) in mice receiving memory Th2 cells. In contrast, the same treatment induced only airway inflammation but not AHR in mice receiving memory Th1 cells. However, these mice developed striking AHR when they were coadministered with IL-18. Furthermore, mice having received IFN-γ–expressing Th1 cells sorted from polarized Th1 cells developed severe airway inflammation and AHR after intranasal administration of Ag and IL-18. Thus, Th1 cells become harmful when they are stimulated with Ag and IL-18. Newly polarized Th1 cells and IFN-γ–expressing Th1 cells, both of which express IL-18 receptor α chain strongly, produce IFN-γ, IL-9, IL-13, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor α, regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein 1α upon stimulation with Ag, IL-2, and IL-18 in vitro. Thus, Ag and IL-18 stimulate memory Th1 cells to induce severe airway inflammation and AHR in the naive host.

scholarly journals NF-κB and AP-1 Activation by Nitric Oxide Attenuated Apoptotic Cell Death in RAW 264.7 Macrophages

1999 ◽  
Vol 10 (2) ◽  
pp. 361-372 ◽  
Author(s):  
Andreas von Knethen ◽  
Dagmar Callsen ◽  
Bernhard Brüne
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Low Dose ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Raw 264.7 ◽  
Raw 264.7 Macrophages ◽  
Low Level ◽  
Ifn Γ ◽  
Cox 2

A toxic dose of the nitric oxide (NO) donorS-nitrosoglutathione (GSNO; 1 mM) promoted apoptotic cell death of RAW 264.7 macrophages, which was attenuated by cellular preactivation with a nontoxic dose of GSNO (200 μM) or with lipopolysaccharide, interferon-γ, and NG-monomethyl-l-arginine (LPS/IFN-γ/NMMA) for 15 h. Protection from apoptosis was achieved by expression of cyclooxygenase-2 (Cox-2). Here we investigated the underlying mechanisms leading to Cox-2 expression. LPS/IFN-γ/NMMA prestimulation activated nuclear factor (NF)-κB and promoted Cox-2 expression. Cox-2 induction by low-dose GSNO demanded activation of both NF-κB and activator protein-1 (AP-1). NF-κB supershift analysis implied an active p50/p65 heterodimer, and a luciferase reporter construct, containing four copies of the NF-κB site derived from the murine Cox-2 promoter, confirmed NF-κB activation after NO addition. An NF-κB decoy approach abrogated not only Cox-2 expression after low-dose NO or after LPS/IFN-γ/NMMA but also inducible protection. The importance of AP-1 for Cox-2 expression and cell protection by low-level NO was substantiated by using the extracellular signal-regulated kinase inhibitor PD98059, blocking NO-elicited Cox-2 expression, but leaving the cytokine signal unaltered. Transient transfection of a dominant-negative c-Jun mutant further attenuated Cox-2 expression by low-level NO. Whereas cytokine-mediated Cox-2 induction relies on NF-κB activation, a low-level NO–elicited Cox-2 response required activation of both NF-κB and AP-1.

scholarly journals Expression of the Nitric Oxide Synthase 2 Gene Is Not Essential for Early Control of Mycobacterium tuberculosis in the Murine Lung

2000 ◽  
Vol 68 (12) ◽  
pp. 6879-6882 ◽  
Author(s):  
Andrea M. Cooper ◽  
John E. Pearl ◽  
Jason V. Brooks ◽  
Stefan Ehlers ◽  
Ian M. Orme
Keyword(s):  
Nitric Oxide ◽  
Mycobacterium Tuberculosis ◽  
Nitric Oxide Synthase ◽  
Low Dose ◽  
Interleukin 12 ◽  
Infection Model ◽  
Rapid Progression ◽  
Ifn Γ ◽  
Nitric Oxide Synthase 2 ◽  
Oxide Synthase

ABSTRACT The interleukin-12 and gamma interferon (IFN-γ) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-γ-activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controllingMycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a low dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-γ or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-γ is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene.

scholarly journals Effect of vitamin D3 on lung damage induced by cigarette smoke in mice

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 827-832
Author(s):  
Xin Zheng ◽  
Nini Qu ◽  
Lina Wang ◽  
Guoli Wang ◽  
Rui Jiao ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Vitamin D3 ◽  
Lung Diseases ◽  
Low Dose ◽  
Lung Damage ◽  
Over Expression ◽  
Ifn Γ ◽  
Airway Model ◽  
Morphological Assessment

AbstractCigarette smoking is known to induce serious lung diseases, but there is not an effective method to solve this problem. The present study investigated vitamin D3 on over-expression of CXCR3 and CXCL10 in mice induced by cigarette smoking. A pulmonary airway model was designed, and morphological assessment of emphysema, IL-4, IFN-γ and CXCL10 concentration in bronchoalveolar lavage fluids, expression of CXCR3 and CXCL10 were detected. Emphysema of the mice only exposed to cigarette smoke was significant, and concentration of IL-4, IFN-γ and CXCL10 was also increased. In addition, CXCR3 and CXCL10 were over-expressed. The degree of emphysema, concentration of IL-4, IFN-γ and CXCL10, and expression of CXCR3 and CXCL10 in mice administrated with low dose vitamin D3 were similar to the normally treated mice. Low dose of vitamin D3 can effectively protect the lung from the damage induced by cigarette smoke.

Sign in / Sign up

Export Citation Format

Share Document