Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Food allergy is an important and common health issue, and there is a need to identify and characterize the sensitizing mechanisms. One of the common causes of food allergy is ovalbumin (OVA), a dietary antigen from eggs. We hypothesized that OVA-induced food allergy in the gut involves the activation of the chemokine regulated on activation, normal T cell expressed and secreted (RANTES), which then recruits eosinophils to lesioned tissue. The purpose of this study was to clarify whether RANTES expression correlates with eosinophil infiltration in the gut of OVA-sensitized BALB/c mice in response to oral OVA challenge. BALB/c mice were immunized with OVA 1 microg and sensitized after 2 weeks by intragastric administration of OVA. Sensitization to the oral OVA challenge was analyzed by examining eosinophil infiltration into the gut tissue (immunohistochemistry), mucosal eosinophil cationic protein (ECP) concentration, and RANTES mRNA expression (reverse-transcriptase polymerase chain reaction and Southern blotting) at 3, 6, 12, and 24 h after the challenge. There was marked edema of the intestinal villi, and eosinophil infiltration to the lamina propria peaked at 6 h in OVA-sensitized mice. RANTES mRNA expression peaked at 3 h and 6 h and declined thereafter. The expression of RANTES mRNA in the allergic mice was much higher than in the nonallergic, normal, or unsensitized control mice. Tissue eosinophilia and intestinal ECP levels were significantly correlated with the RANTES mRNA level. We conclude that RANTES may play a central role in the pathogenesis of food-mediated gastrointestinal allergy.
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PMID:The role of RANTES in a murine model of food allergy. 1501 30

The initiation mechanism of IgE expression has not been fully understood. Flagellin (FGN) is an important microbial factor in the regulation of immune responses in the intestine. This study tests a hypothesis that FGN plays a crucial role in the isotype switching of IgE in B cells and the initiation of food allergy. In this study, the expression of IgE in B cells was analyzed by real time RT-PCR, Western blotting and chromatin immunoprecipitation. A mouse model was developed to assess the role of Toll like receptor-5 in the development of IgE-mediated allergic reaction in the intestinal mucosa. The results showed that exposure to FGN suppressed the expression of Bcl6 in B cells via increasing the levels of histone deacetylase (HDAC) 7; the latter up regulated the levels of methylated H3K9 and H3K27, down regulated RNA polymerase II and STAT3 (signal transducer and activator of transcription 3) at the Bcl6 promoter locus. Exposure to FGN and IL-4 markedly increased the expression of IgE in B cells via activating p300, H3K4, Pol II and STAT6 at the IgE promoter locus. As compared with the sensitized wild mice, the sensitized TLR5-deficient mice showed no detectable OVA-specific IgE in the serum; mast cells in the intestinal mucosa were not activated, no apparent allergic symptoms were evoked after the specific antigen challenge. In conclusion, FGN facilitates the initiation of food allergy in mice by triggering IgE transcription in B cells in a Th2 polarization environment via activating HDAC7 and suppressing Bcl6 expression.
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PMID:Flagellin modulates IgE expression in B cells to initiate food allergy in mice. 2739 57

Allergic disorders include food allergy, allergic rhinitis, and certain forms of asthma resulting from the inappropriate development of immune responses to otherwise innocuous aeroallergens and foods. In this issue of the JCI, Thouvenot and Roitel et al. explore transcription infidelity as a mechanism that underlies the ability of these benign proteins to become allergens. Some foods and bioaerosols that produce allergies have RNA polymerase with a propensity to generate RNA gaps, thereby causing translational frameshifts. These frameshifts often create cationic carboxy-terminus residues that replace hydrophobic amino acids and have enhanced MHC binding, resulting in the tendency to provoke immune responses. IgE antibody responses initiated by these variant transcripts can later lead to IgE against the native molecule and also explain how anaphylaxis may occur in individuals who lacked specific IgE when tested using native protein reagents. This study has the potential to transform the diagnosis and treatment of allergic disorders.
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PMID:Insights into how innocuous foods or proteins deserving of immune ignorance can become allergens. 3295 89