Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in Prevotella and Lactobacillus, while decreasing Sutterella and Bacteroides. Fecal transplants from TCDD-treated donor mice into antibiotic-treated mice induced MDSCs and increased regulatory T-cells (Tregs). Injecting TCDD directly into antibiotic-treated mice also induced MDSCs, although to a lesser extent. These data suggested that TCDD-induced dysbiosis plays a critical role in MDSC induction. Interestingly, treatment with TCDD led to induction of MDSCs in the colon and undetectable levels of cysteine. MDSCs suppressed T cell proliferation while reconstitution with cysteine restored this response. Lastly, blocking CXC chemokine receptor 2 (CXCR2) impeded TCDD-mediated MDSC induction. Our data demonstrate that AhR activation by TCDD triggers dysbiosis which, in turn, regulates, at least in part, induction of MDSCs.
The compound 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an environmental contaminant, is a potent ligand for aryl hydrocarbon receptor (AhR). In the current study, we made an exciting observation that naive C57BL/6 mice that were exposed i.p. to TCDD showed massive mobilization of myeloid-derived suppressor cells (MDSCs) in the peritoneal cavity. These MDSCs were highly immunosuppressive and attenuated Con A–induced hepatitis upon adoptive transfer. TCDD administration in naive mice also led to induction of several chemokines and cytokines in the peritoneal cavity and serum (CCL2, CCL3, CCL4, CCL11, CXCL1, CXCL2, CXCL5, CXCL9, G-CSF, GM-CSF, VEGF, and M-CSF) and chemokine receptors
Asthma is a condition characterized by bronchial spasms, inflammation, and mucous hypersecretion which leads to difficulties in respiration. Asthmatic patients are usually presented with recurrent attacks of coughing, wheezing, and shortness of breath which could be life-threatening. More than three million cases of asthma in the United States are diagnosed annually. Resveratrol, a polyphenolic stilbene, is known to be useful in controlling asthmatic attacks via different molecular mechanisms within the lung epithelium and infiltrating immune cells. However, few studies mentioned the effect of resveratrol on the microbiome in ovalbumin-induced asthma mouse model. In this study, we ind
Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates T cell function. The aim of this study was to investigate the effects of AhR ligands, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), and 6-Formylindolo[3,2-b]carbazole (FICZ), on gut-associated microbiota and T cell responses during delayed-type hypersensitivity (DTH) reaction induced by methylated bovine serum albumin (mBSA) in a mouse model. Mice with DTH showed significant changes in gut microbiota including an increased abundance of
In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species in an iron-dependent manner.
BACKGROUND: Hepatocyte growth factor (HGF) is a proangiogenic factor that exerts different effects over stem cell survival growth, apoptosis, and adhesion. Its impact on leukemogenesis has been established by many studies. AIM: This study aimed to determine the effect of plasma HGF activity on acute myeloid leukemia (AML) patients at presentation and after remission. PATIENTS AND METHODS: This was a cross-sectional prospective study of 30 newly-diagnosed, adult, and AML patients. All patients received the 7+3 treatment protocol. Patients’ clinical data were taken at presentation, and patients were followed up for 6 months to evaluate the clinical status. Plasma HGF levels were estimated by ELISA based methods in the pa
... Show MoreThe recurrent somatic variations in
The aim of the study was to detect the frequency of R132 mutations in the
Background: Healing of a tooth extraction socket is a complex process involving tissue repair and regeneration. It involves chemotaxis of appropriate cells into the wound, Transformation of undifferentiated mesenchymal cells to osteoprogenitor cells, proliferation and differentiation of committed bone forming cells, extracellular matrix synthesis, mineralization of osteoid, maturation and remodeling of bone. These cellular events are precisely controlled and regulated by specific signaling molecules. Some of these like transforming growth factor beta (TGF-?), vascular endothelial growth factor (VEGF), bone morphogenetic proteins (BMP) and insulin like growth factors (IGF) are well conserved proteins involved in the initial response to injur
... Show MoreAbstract Background: Acute myeloid leukemia (AML) results from sequential genetic alterations in a normal hematopoietic stem cell or its progenitors giving rise to an autonomous clone that dominates the bone marrow leading to marrow failure. MicroRNAs are short non-coding nucleic acid sequences that regulate post-transcriptional gene expression by base-pairing with their target mRNAs. MiRNAs can be secreted into extracellular fluids and carried to target cells by vesicles or bound to proteins. Intracellular and circulating miRNAs are believed to be useful markers in the diagnosis, prognosis, and treatment of various cancers. Practically, circulating miRNAs are more stable at room temperatures and extreme conditions. Purpose: This study aim
... Show MoreThe study aimed to compare the expression of miR-126-3p and miR-423-5p in patients and normal subjects, and correlate their expression with response to induction therapy. Circulating miR-126-3p and miR-423-5p were measured in the plasma of 43 adult AML patients and 35 age- and sex-matched controls by real time PCR. The foldchange in differential expression for each gene was calculated using the comparative cycle threshold (CT) method (also known as the 2−CT method). For statistical purposes, the fold change was calculated using DDCT (or 2–∆∆Ct) method to find the relative expression of miRNAs. The expression fold change of miR-126-3p was 1.73-fold increase in patients than controls (p= 0.010). The expression fold change of miR-423-5
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