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Dysregulated Immune Response (dysregulated + immune_response)
Selected AbstractsUbiquitin protein modification and signal transduction: Implications for inflammatory bowel diseasesINFLAMMATORY BOWEL DISEASES, Issue 12 2005Cormac Taylor PhD Abstract A dysregulated immune response to luminal antigen(s) is associated with the development of inflammatory bowel diseases (IBDs). A complex network of inflammatory and immune mediators released by immune and nonimmune cells participate in the physiopathology of IBD. At the molecular level, events leading to the improper use of the signaling grid are likely responsible for the dysregulated activation of various transcription factors and subsequent induction of inflammatory genes. The posttranslational modification of signaling proteins by the ubiquitin system is a critical event in activation or repression of transcription factors. Two important transcriptional pathways in which ubiquitin is central are the nuclear factor-,B and hypoxia inducible factor-1 (HIF-1) pathways, both of which are important components of intestinal homeostasis. In this review, we discuss the role of ubiquitin modification in relation to nuclear factor-,B and HIF-1 signaling and consider its impact on intestinal inflammation. A greater understanding of posttranslational ubiquitin modification may lead to the identification of new therapeutic opportunities for the treatment of IBD. [source] Oxidative stress and metabolism in animal model of colitis induced by dextran sulfate sodiumJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2007Carlos R Damiani Abstract Background and Aim:, Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal tract. Its etiology remains unclear, but it appears to result from a dysregulated immune response, with infiltration of phagocytic leukocytes into the mucosal interstitium. The production and release of reactive oxygen species by immune cells seems to play a crucial role in physiopathology of colitis. The aim of this work was to evaluate the effects of N-acetylcysteine (NAC) and deferoxamine (DFX) in the treatment of colitis induced by dextran sulfate sodium (DSS). Methods:, The effects of NAC and DRX on rats with DSS-induced colitis were determined by measuring intestinal parameters of oxidative stress and mitochondrial function, inflammatory response and bowel histopathological alterations. Results:, DSS increased white blood cells count and NAC and DFX did not prevent this effect. However, DSS increased mitochondrial respiratory chain complex IV in colon of rats and NAC and DFX prevented this alteration. In addition, thiobarbituric acid reactive substances were increased in colon of DSS-treated rats. NAC and DFX, when taken together, prevented this effect. Complex II and succinate dehydrogenase were not affected by DSS, as protein carbonyl content. Conclusions:, It is speculated that NAC and DFX might be useful for treatment of colitis, but further research is necessary to clarify these effects. [source] Suppression of proinflammatory cytokines and induction of IL-10 in human monocytes after coxsackievirus B3 infectionJOURNAL OF MEDICAL VIROLOGY, Issue 4 2001P. Hofmann Abstract Coxsackievirus B3 (CVB3) causes acute and chronic myocarditis, which is accompanied by an intense mononuclear leukocyte infiltration. Because myocardial tissue damage may either result from viral infections or from a dysregulated immune response, the susceptibility of human monocytes and macrophages to CVB3 was examined in this study with regard to virus replication, virus persistence, and release of cytokines. Monocytes were infected by CVB3 as shown by the intracellular appearance of plus- and minus-strand viral RNA, which was also capable of persisting for more than 10 days. Fresh monocytes were not permissive for full virus replication whereas monocyte-derived macrophages yielded a low amount of new viruses, which led to cell death. Although CVB3 infection induced the mRNA for the proinflammatory cytokines tumor necrosis factor-alpha (TNF-,), interleukin (IL)-1, and IL-6, only little cytokine production occurred. When infected monocytes were stimulated in addition by lipopolysaccharides (LPS), cytokine production was partially suppressed. In striking contrast, IL-10 expression was strongly and persistently induced by CVB3 on the mRNA and the protein level. These data show a dysregulated cytokine response in CVB3-exposed human monocytes and macrophages, which is characterized by a suppression of proinflammatory cytokines and a dominance of IL-10. This viral strategy may aid CVB3, causing chronic myocardiopathy. J. Med. Virol. 64:487,498, 2001. © 2001 Wiley-Liss, Inc. [source] Enhanced levels of cow's milk antibodies in infancy in children who develop type 1 diabetes later in childhoodPEDIATRIC DIABETES, Issue 5 2008Kristiina Luopajärvi Background:, Early exposure to cow's milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). Objective:, We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. Subjects and methods:, We studied a subgroup of 94 children randomized to be weaned to a CM-based infant formula in the trial to reduce insulin-dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen-conferred T1D susceptibility and had an affected first-degree relative. After 7 years of follow-up, 8 subjects had progressed to T1D, 15 had at least one disease-associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta-lactoglobulin (BLG), bovine serum albumin, and alpha-casein and IgG antibodies to bovine insulin (BI) were measured with enzyme-linked immunosorbent assays from sequential samples. Results:, The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody-positive subjects than in autoantibody-negative subjects at 18 months of age (p = 0.022). Conclusion:, An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D. [source] Patterns of immunoglobulin G responses to egg and peanut allergens are distinct: ovalbumin-specific immunoglobulin responses are ubiquitous, but peanut-specific immunoglobulin responses are up-regulated in peanut allergyCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2007S. S. Tay Summary Background The clinical significance of food-specific IgG subclasses in food allergy and tolerance remains unclear. Specific IgG titres are often reported in non-standardized units, which do not allow comparisons between studies or allergens. Objective To quantify, in absolute units, ovalbumin (OVA)- and peanut-specific IgG levels in children with peanut or egg allergy (active or resolved) and in non-allergic controls. Methods Children aged 1,15 years were recruited. Peanut allergy was diagnosed by convincing history and a 95% predictive level of specific IgE; egg allergy or resolution was confirmed by oral challenge. Serum IgG, IgG1 and IgG4 levels (,g/mL) to OVA and peanut extract were quantified by ELISA. Results OVA- and peanut-specific IgG was detected in all subjects. In non-allergic controls (n=18), OVA-specific IgG levels were significantly higher than peanut-specific IgG (median ,g/mL IgG=15.9 vs. 2.2, IgG1=1.3 vs. 0.6, IgG4=7.9 vs. 0.7; P<0.01). There were no differences in OVA-specific IgG, IgG1 and IgG4 between egg-allergic (n=40), egg-resolved (n=22) and control (n=18) subjects. In contrast, peanut-specific IgG (median ,g/mL IgG=17.0, IgG1=3.3, IgG4=5.2) were significantly higher in peanut-allergic subjects (n=59) compared with controls and with non-peanut-sensitized but egg-allergic subjects (n=26). Overall, the range of IgG4 was greater than IgG1, and IgG4 was the dominant subclass in >60% of all subjects. Conclusion OVA-specific IgG levels of egg-allergic, egg-resolved or control groups are not distinguishable. Higher peanut-specific IgG levels are associated with clinical allergy, but the range of IgG titres of the allergic and control groups overlapped. Hence, OVA and peanut-specific IgG measurements do not appear to be of diagnostic value. Strong IgG responses to OVA may be a normal physiological response to a protein frequently ingested from infancy, whereas up-regulated IgG responses in peanut allergy may be indicative of a dysregulated immune response to peanut allergens. [source] | ||||||||||