Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-4Ralpha-mediated STAT6 activation serves an essential role in various animal models of allergy and asthma at both the sensitization and effector phases. IL-4 and IL-13 signaling via the IL-4Ralpha chain exacerbates murine anaphylaxis, but the cell-specific requirements for IL-4Ralpha expression are unclear. The purpose of this study was to elucidate the mechanisms of systemic anaphylaxis to OVA in gene-targeted mice with a deletion of the IL-4Ralpha chain in the macrophage/neutrophil or CD4+ T lymphocyte population. Results demonstrated that anaphylaxis in this model was entirely dependent upon the FcgammaRII/III and was associated with mast cell degranulation. Expression of the IL-4Ralpha on CD4+ T cells, but not macrophages or neutrophils, was critical for severe anaphylaxis, characterized by diarrhea, hypothermia, and death. Ab depletion experiments demonstrated that IFN-gamma protected against mortality and severe intestinal pathology despite the presence of Ag and specific Ab. This protection was associated with reduced levels of mast cell protease, a marker of mast cell degranulation, suggesting that IFN-gamma may inhibit mast cell degranulation in vivo. These data suggest that it may be possible to limit the severity of anaphylaxis using rational therapies designed to increase numbers of IFN-gamma-producing cells by targeting IL-4Ralpha signaling in CD4+ T lymphocytes.
 ...
PMID:CD4+ T cell-specific deletion of IL-4 receptor alpha prevents ovalbumin-induced anaphylaxis by an IFN-gamma-dependent mechanism. 1770 89

We investigated malaria-associated pathology in mice co-infected with Heligmosomoides polygyrus (Hp) and Plasmodium chabaudi AS (Pc). Despite higher peak parasitemia, co-infected wild-type (WT) C57BL/6 mice displayed similar body weight losses, malarial anaemia, and tissue damage but less severe hypothermia and hypoglycaemia, and earlier reticulocytosis than Pc-infected WT mice. Co-infected STAT6(-/-) mice, deficient in nematode-induced Th2 responses, experienced similar peak parasitemias and generally suffered malaria-associated pathology to a similar degree as co-infected WT mice. These data indicate a complex relationship amongst helminths, malaria and host immune responses resulting in modulation of some but not all aspects of malaria-associated pathology.
 ...
PMID:Modulation of malaria-induced immunopathology by concurrent gastrointestinal nematode infection in mice. 1971 71

T cell peptide-based immunotherapy (PIT) is an appealing therapeutic strategy for modulating allergic responses without IgE cross-linking. We propose a novel PIT that combines a T-cell epitope of the shrimp allergen arginine kinase (AKp) with TLR9 agonist CpG-ODN in nanoparticles (CpG-AKp NPs) to attenuate a shrimp allergen-induced food allergy. Treatment with CpG-AKp NPs demonstrated the attenuation of anaphylaxis responses such as the reduced incidence of diarrhea and hypothermia, lower levels of specific IgE and the induction of IgG2a in serum. Th2 cytokines were suppressed and higher Th1 cytokines were detected in the splenocyte culture supernatants. Treatment of CpG-AKp NPs also enhanced the protein expression of Foxp3 and IL-10 in small intestine but decreased the activation of STAT6 and GATA3 expression, which are related to differentiation of Th2. Our data indicated that CpG-AKp NPs may represent a promising PIT against shrimp allergy.
 ...
PMID:T cell epitope of arginine kinase with CpG co-encapsulated nanoparticles attenuates a shrimp allergen-induced Th2-bias food allergy. 3182 91

Brown adipose tissue generates heat via the mitochondrial uncoupling protein UCP1 to protect against obesity and hypothermia. Fas mutant MRL/lpr mice exhibit a significantly leaner phenotype compared to wild type MRL/MpJ mice. In this study, we evaluated the inflammatory cell population in the adipose tissue of MRL/lpr mice, which could potentially influence their lean phenotype. Furthermore, we compared beige fat activity between the MRL/MpJ and MRL/lpr mice. Fas mutation resulted in high body temperature, improved glucose tolerance, and decreased fat mass and adipocyte size. Fas mutation prevented high-fat diet-induced obesity and decreased the white adipose tissue M1:M2 ratio. When mice were fed a high-fat diet, UCP1, IL-4, IL-10, and tyrosine hydroxylase genes had significantly higher expression in Fas-mutant mice than in wild type mice. After a cold challenge, UCP1 expression and browning were also significantly higher in the Fas-mutant mice. In summary, Fas-mutant mice are resistant to high-fat diet-induced obesity due to increased IL-4 and IL-10 levels and the promotion of thermogenic protein activity and browning in their adipose tissues. STAT6 activation might contribute to M2 polarisation by increasing IL-4 and IL-10 levels while increases in M2 and tyrosine hydroxylase levels promote browning in response to Fas mutation.
 ...
PMID:Fas mutation reduces obesity by increasing IL-4 and IL-10 expression and promoting white adipose tissue browning. 3268 63