bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin E‐binding and skin test reactivity to hydrophobin HCh‐1 from Cladosporium herbarum, the first allergenic cell wall component of fungi
Authors: Weichel M. , Schmid‐Grendelmeier P. , Rhyner C. , Achatz G. , Blaser K. , Crameri R. 
Published: March 2003

SummaryBackground For many years, fungal spores have been recognized as potential causes of respiratory allergies. All fungal allergens cloned so far represent either secreted or cytoplasmatic proteins, but nothing is known about the involvement of fungal surface proteins in allergic diseases.Methods A phage surface displayed cDNA‐library from the mould Cladosporium herbarum was constructed and phage displaying IgE‐binding proteins were selectively enriched with immobilized serum IgE from C. herbarum‐sensitized individuals. Inserts encoding putative allergens were sequenced, subcloned and used to produce recombinant proteins. Allergenicity of the proteins was evaluated by IgE binding in Western blots, enzyme‐linked immunosorbent assay (ELISA) and skin prick test in a total of 84 patients sensitized to either C. herbarum or Aspergillus fumigatus and three healthy controls.Results After four rounds of affinity selection, the cDNA‐library was enriched for clones displaying IgE‐binding molecules. Sequencing of inserts showed that one clone contained an open reading frame predicting a protein of 105 amino acids and a calculated molecular weight of 10.5 kDa showing the classical signature of members of the hydrophobin family. The recombinant protein, termed HCh‐1, was able to bind IgE from six patients sensitized to fungi in vitro. Two of those patients were also included in a skin prick test survey and showed strong type I skin reactions to HCh‐1, demonstrating the allergenic nature of C. herbarum hydrophobin and indicating a prevalence of sensitization in the range of 8–9%. In contrast, the hydrophobin HYP1 from Aspergillus fumigatus was not recognized by the sera of the same patients and controls investigated with HCh‐1.Conclusion C. herbarum hydrophobin represents the first component of the cell wall of fungi demonstrated to act as a rare but clinically relevant allergen in vitro and in vivo.
Suppression of allergic reaction by λ‐carrageenan: Toll‐like receptor 4/MyD88‐dependent and ‐independent modulation of immunity
Authors: Tsuji R. F. , Hoshino K. , Noro Y. , Tsuji N. M. , Kurokawa T. , Masuda T. , Akira S. , Nowak B. 
Published: March 2003

SummaryBackground Recognition of foreign substances by innate immunity through pattern recognition receptors (PRRs) regulates acquired immunity such as allergic reaction. Because PRRs recognize heterogeneous ligands, daily food intake can potentially regulate immune allergic reaction.Objective Elucidation of the effect of λ‐carrageenan on allergic reactions was aimed.Method IFN‐γ and IL‐4 was measured in in vitro T cell‐stimulated culture. Cytokine production from macrophages in response to λ‐carrageenan was measured as indicator for innate immunity activation. Mice were immunized with OVA in alum to induce specific IgE, and then histamine release was induced by systemic injection of OVA.Results Activation of innate immunity by λ‐carrageenan is dependent on Toll‐like receptor‐4 (TLR4) and MyD88, in which induction of pro‐inflammatory cytokines such as TNF‐α and IL‐6 was largely impaired in macrophages from TLR4‐ and MyD88‐deficient mice. Footpad oedema, a model for in vivo inflammatory reactions, was significantly reduced in these mice. Similar to recent evidence showing a preference for the stimulation of Th1 via TLR/MyD88 signalling, λ‐carrageenan showed enhanced IFN‐γ and decreased IL‐4 in stimulated T cell cultures. Interestingly, increased IFN‐γ production was still seen in TLR4‐ and MyD88‐deficient splenocytes. Oral administration of λ‐carrageenan to immunized mice successfully decreased OVA‐specific IgE, and λ‐carrageenan was also effective in previously immunized mice. Further, serum histamine release upon systemic challenge of OVA was significantly inhibited. Neither OVA‐specific IgG1/IgG2a nor cytokine secretion from in vitro cultures were altered, suggesting the involvement of multiple PRRs as demonstrated by TLR4/MyD88‐independent IFN‐γ up‐regulation. The simultaneous feeding of OVA with lipopolysaccharide abrogated oral tolerance, but λ‐carrageenan was not only devoid of such an effect but was also found to promote oral tolerance in the absence of TLR4.Conclusion λ‐Carrageenan was suggested to be a useful dietary supplement to ameliorate allergic reactions while maintaining oral tolerance‐dependent intestinal homeostasis.
Interleukin‐10 gene promoter region polymorphism is associated with eosinophil count and circulating Immunoglobulin E in adult asthma
Authors: Karjalainen J. , Hulkkonen J. , Nieminen M. M. , Huhtala H. , Aromaa A. , Klaukka T. , Hurme M. 
Published: March 2003

SummaryBackground IL‐10 has several functional effects relevant to asthma. It can modulate IgE production and induce apoptosis in eosinophils. Polymorphisms of IL‐10 gene have been shown to affect IL‐10 production.Objective To establish whether IL‐10 polymorphisms are associated with asthma and phenotype‐related characteristics.Methods The frequency of three single base exchange polymorphisms (at positions − 1082, − 819 and − 592) and corresponding haplotypes of the IL‐10 gene were analysed in 245 adult asthmatic subjects and 405 controls using PCR and restriction fragment length polymorphism (RFLP). The data were assessed for correlations with the eosinophil count, serum IgE and lung function.Results The IL‐10 haplotype frequencies were similar in asthmatics and controls. Eosinophil count median was 2.0‐ to 3.2‐fold higher among asthmatics with rare ATA/ATA genotype than in asthmatics with other genotypes. No such difference was seen in the control group. When analysed by IL‐10 haplotype carrier state and gender, male asthmatics with ATA haplotype had 2.8‐fold higher serum IgE than those without ATA. A converse association was found in male controls with ATA haplotype, who had 1.9‐fold lower serum IgE than their ATA‐negative counterparts. The high IL‐10‐producing GCC haplotype was associated with impaired lung function in smoking male controls while in asthmatics no clear effect on lung function was found with any of the haplotypes studied.Conclusion These results suggest that the eosinophil counts and serum IgE are differently regulated by IL‐10 genotype in asthmatic and in normal subjects. However, IL‐10 polymorphism is not related to susceptibility in asthma.
Familial and environmental determinants for wheezing and asthma in a case‐control study of school children in Palestine
Authors: El‐Sharif N. , Abdeen Z. , Barghuthy F. , Nemery B. 
Published: March 2003

SummaryBackground Our prevalence study on Palestinian school children aged 6–12 years showed lower rates for asthma and asthma symptoms than economically developed and industrialized countries. Reasons for such differences are largely unknown, and could possibly be related to different environmental and lifestyle factors.Objective To investigate familial, early life exposures and indoor environmental determinants for asthma in children in Palestine.Methods From the population of our previous study, a group of 273 children with wheeze in the past 12 months (of whom 99 children had physician‐diagnosed asthma) were matched with an equal number of non‐wheezing controls. This case‐control study involved a parental questionnaire; skin prick testing (SPT) with mixed house dust mites, cat and dog dander, mixed grass, mixed trees pollen, Alternaria tenuis, olive tree and cockroach extracts; and serum for total and specific IgE for the same eight allergens.Results Paternal asthma and maternal hayfever significantly tripled the risk for their children to have wheezing. Previous diagnoses of bronchial allergy, bronchitis, pneumonia, or whooping cough, and positive SPT for house dust mites and cockroaches were significantly more likely among wheezing and asthmatic children than controls. Specific IgE levels for house dust mites and cat allergens showed significantly higher risk for reported wheezing. After adjustment for several environmental and sociodemographic factors using multivariate logistic regression analysis, paternal asthma, maternal hayfever, damp houses, cat and cockroach SPT positivity proved to be strong predictors for wheezing symptoms.Conclusion Our study confirmed that familial ‘atopic’ diseases are significant predictors of childhood asthma in Palestinian children. Moreover, indoor environment such as presence of cats and domestic moulds also appear to play a role. Our findings are consistent with studies in Canada, New Zealand, Estonia and Sweden, and show promise to explore further gene–environment interaction in the genesis of asthma.
Pathogenesis of autoimmunity in αβ T cell-deficient lupus-prone mice
Authors: Peng S L , Cappadona J , Mcniff J M , Madaio M P , Owen M J , Hayday A C , Craft J 
Published: March 2003

AbstractMurine lupus in MRL mice has been strongly attributed to αβ T cell-dependent mechanisms. Non-αβ T cell-dependent mechanisms, such as γδ T cells, have been shown to drive antibody and autoantibody production, but they have not been considered capable of inducing end-organ disease. Here, we have expanded upon the findings of such previous work by examining the mechanism and extent of end-organ disease attainable via γδ T cells and/or non-αβ T cell-dependent mechanisms, assessing two prototypical lupus lesions, renal and skin disease, in TCR α−/− MRL mice that possessed either functional or defective Fas antigen (Fas + or lpr). Observed to 1 year of age, TCR α−/− MRL mice developed disease characterized by increased mortality, overt renal disease and skin lesions. While delayed in onset and/or reduced in severity compared with TCR α+/+ MRL/lpr animals, renal and skin lesions in αβ T cell-deficient animals were clearly increased in severity compared with age-matched control non-autoimmune mice. In contrast to TCR α+/+ MRL mice, whose disease reflected pan-isotype immune complex deposition with significant complement fixation, renal disease in TCR α−/− MRL animals reflected predominantly IgG1 immune complex deposition, with poor complement fixation. Thus, this study demonstrates conclusively that non-αβ T cell-dependent mechanisms can induce renal and skin injury in murine lupus, but at least in the kidney, only via humoral autoimmunity of a relatively non-pathological isotype which results in the delayed onset of end-organ damage.
IL-15 mRNA expression is up-regulated in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis (MS)
Authors: Kivisäkk P , Matusevicius D , He B , Söderström M , Fredrikson S , Link H 
Published: March 2003

AbstractIL-15, produced by monocytes and epithelial cells, is a novel cytokine with actions similar to IL-2. IL-15 induces T cell proliferation, B cell maturation and natural killer (NK) cell cytotoxicity, and is a chemoattractant for T cells. We investigated the expression of IL-15 mRNA in blood and cerebrospinal fluid (CSF) mononuclear cells (MNC) in MS, an inflammatory disease of the central nervous system where cytokines are involved. MS patients had higher numbers of IL-15 mRNA-expressing blood MNC than patients with aseptic meningo-encephalitis (AM) and healthy controls. In CSF, MS patients had even higher numbers of IL-15 mRNA-expressing cells than in blood. This discrepancy between IL-15 mRNA expression between blood and CSF MNC was not seen in AM patients. Patients examined during the secondary chronic-progressive phase of MS had higher numbers of IL-15 mRNA-expressing blood MNC compared with patients examined during the relapsing-remitting phase. Levels of IL-15 mRNA-positive blood MNC were similar in patients with AM, myasthenia gravis, non-inflammatory neurological diseases and healthy controls. Taken together these data indicate that IL-15 mRNA expression is up-regulated in MS, further suggesting a role for proinflammatory cytokines in the pathogenesis of MS.
Th1/Th2 cytokine responses following HIV-1 immunization in seronegative volunteers
Authors:   THE AIDS VACCINE EVALUATION GROUP, Evans T G , Fitzgerald T , Gibbons D C , Keefer M C , Soucier H 
Published: March 2003

SUMMARYThe Th1/Th2 profile that follows human vaccination may profoundly influence the subsequent course of disease after infection. However, the ability to detect IL-4 has been limited outside trials of live vaccination. By using methods in which memory effector cells are allowed to antigenically expand by short term culture, followed by low-dose mitogenic stimulation, we have been able to follow the Th1/Th2 profile in HIV-1−volunteers enrolled in two phase I studies of HIV immunogens (a recombinant gp120 and a multivalent, octomeric V3 loop peptide). Antigen-specific interferon-gamma (IFN-γ) could be detected in primary stimulation, but IL-4 was observed only after antigenic expansion and restimulation. In both of these studies the responses after initial immunizations were dominated by IFN-γ, with IL-4 appearing only after multiple rounds of immunization, and IL-4 was temporally related to antibody production. Concomitant with the IL-4 production, the amount of supernatant IFN-γ declined. Antigen-specific IL-10 was not detected in either study. Such techniques, which have been shown to correlate with outcomes in immunotherapy, may prove useful as future surrogates of human vaccine response.
Prevalence and characterization of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) directed against HMG1 and HMG2 in ulcerative colitis (UC)
Authors: Sobajima J , Ozaki S , Uesugi H , Osakada F , Shirakawa H , Yoshida M , Nakao K 
Published: March 2003

SUMMARY
In a previous study, we reported that the high mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 were novel target antigens of P-ANCA. In this study, we determined the immunodiagnostic value of anti-HMG1/HMG2 antibodies in patients with UC. Sixty sera from patients with UC were tested for reactivity with HMG1 and HMG2 by means of ELISA. Anti-HMG1 antibody was detected in 32% of patients (40% of P-ANCA+ patients). Anti-HMG2 antibody was detected in 33% (40% of P-ANCA+ patients). Thirty-five percent of sera were positive for antibody to either HMG1 or HMG2 (43% of P-ANCA+ patients). P-ANCA+ patients expressed anti-HMG1/HMG2 antibodies with significantly greater frequency compared with P-ANCA− patients. Furthermore, the anti-HMG1/HMG2 antibodies were significantly related to disease activity in UC. Sixteen of the 18 UC patients, who had high titres of anti-HMG1 or -HMG2 antibody during the active phase, showed lower titres in the inactive phase. Anti-HMG1/HMG2 antibodies appear to be useful as a marker for disease activity in UC.
Relationship between autoantibody epitopic recognition and immunoglobulin gene usage
Authors: Guo J , Mcintosh R S , Czarnocka B , Weetman A P , Rapoport B , Mclachlan S M 
Published: March 2003

SUMMARYAn immunodominant region recognized by serum autoantibodies has been defined on the autoantigen thyroid peroxidase (TPO) using recombinant human TPO-specific Fab or a panel of mouse MoAbs. We have now analysed the epitopic relationships between the four recombinant Fab that identify the A and B domains of the TPO immunodominant region and (i) the mouse TPO MoAb as well as (ii) nine new TPO-specific Fab isolated independently. Competition between mouse MoAbs and recombinant Fab for binding to 125I-TPO revealed three patterns. First, for MoAbs 15, 59, 64 and 18, TPO binding was virtually abolished (≈ 90%) by Fab which define the A domain of TPO, with less inhibition by B domain Fab. Second, for MoAbs 2, 9 and 47, the Fab competed much less for TPO binding, and, when detectable, inhibition was predominantly with B domain Fab (65–20%). Third, for MoAbs 53, 30, 1, 24 and 40, none of the Fab competed effectively for 125I-TPO binding. Thus, the epitopes for MoAbs 18, 59, 64 and 15 correspond to those of the A domain defined by the human Fab, and the epitopes for MoAbs 2, 9 and 47 correspond to those of the B domain. In the second part of the study, competition studies demonstrated that the epitopes of nine new Fab corresponded to those of the four Fab that define the immunodominant region. For four new Fab, TPO binding was inhibited to a greater extent by B- than by A- domain Fab (65–95% versus &lt; 50%). In contrast, for five new Fab the A-domain Fab were more effective inhibitors (≈ 90%) than the B-domain Fab. In addition, consistent with previous observations, all five new Fab with 02/012 κ L chains, but none of the new Fab with non-O2/O12 l chains, interacted with A-domain epitopes. In conclusion, we have established the epitopic relationships between recombinant human Fab and mouse MoAbs that define the TPO immunodominant region on TPO. Further, analysis of recombinant TPO Fab isolated from patients on three continents strengthens the paradigm of a relationship between autoantibody epitopic recognition and immunoglobulin gene usage.
Regulation of secretion of IL-4 and IgG1 isotype by melatonin-stimulated ovalbumin-specific T cells
Authors: Shaji A V , Kulkarni S K , Agrewala J N 
Published: March 2003

AbstractIn the present study, we describe the potential role of melatonin, a pineal hormone, in regulating the activation of the antigen-specific T cell response. Melatonin encouraged the proliferation of Th cells and improved their ability to secrete IL-4, but down-regulated the levels of IL-2 and interferon-gamma (IFN-γ). Melatonin, however, could not exert any influence on the T cells of unprimed mice. On studying the regulation of subclass of IgG isotype, melatonin specifically enhanced the secretion of antigen-specific IgG1 antibodies and decreased the yield of IgG2a isotype. The results suggest that melatonin possibly acts by selectively activating a Th2-like immune response.
Capacity of murine T cells to retain long-term responsiveness to mycobacterial antigens is controlled by theH-2complex
Authors: Pichugin A V , Khaidukov S V , Moroz A M , Apt A S 
Published: March 2003

SUMMARYIt is firmly established that the allelic composition of the H-2 complex has a prominent impact on the course of tuberculosis (TB) infection in mice, including granuloma formation, mycobacterial spread in the lungs, and the dynamics of mortality. Although intuitively obvious, the role of long-term specific T cell responses in the expression of corresponding phenotypes is poorly understood. In this study we have compared polyclonal lymph node cell response (cell yield, proliferation, surface markers, IL-4/interferon-gamma (IFN-γ) production) to Mycobacterium tuberculosis H37Rv sonicate in repeated 10-day cycles of stimulation/rest between H-2 congenic IE-negative mouse strains, categorized on the basis of mortality following lethal challenge as TB-susceptible (C57Bl/6), TB-resistant (4R) and BCG non-protected (B10.M). The capacity to retain specific responsiveness to repeated stimulation by mycobacterial antigens depended upon both the H-2 haplotype of the host and the immunizing dose of the antigen. 4R lymph node cells following either 50 μg/mouse or 100 μg/mouse immunization constantly responded to sonicate, increased in numbers, and after the third stimulation/rest cycle developed into a stable CD3+ CD4+ cell line. B6 cells following either 50 μg/mouse or 100 μg/mouse immunization, and B10.M cells following 100 μg/mouse (but not 50 μg/mouse) immunization, lost the capacity to incorporate methyl-3H-thymidine during the second cycle, and died. Analogous results were obtained in the in vivo experiments, when the dynamics of the response over 12 weeks following a single immunization with the antigen was studied. In response to the antigen, cells from all three mouse strains produced significant amounts of IL-2 and IFN-γ, but not IL-4, indicating that they belong predominantly to the Th1-like subset. Among noteworthy differences between the mouse strains was a clear deficiency of CD8+ T cells in B6 cultures, and an unusually high proportion of CD3+ CD4− CD8− (double-negative) T cells in B10.M cultures following a high-dose immunization.
Regulation of the expression of aminopeptidase A, aminopeptidase N/CD13 and dipeptidylpeptidase IV/CD26 in renal carcinoma cells and renal tubular epithelial cells by cytokines and cAMP-increasing mediators
Authors: Kehlen A , Göhring B , Langner J , Riemann D 
Published: March 2003

SUMMARYAminopeptidase (AP) A is a transmembrane type II molecule widely distributed in mammalian tissues. Since APA expression may be absent in renal cell carcinoma (RCC), it is possible that there is an altered regulation or other defect of APA upon malignant transformation of proximal tubular cells. However, investigations into the regulation of APA on tumour cells are rare. We report, for the first time, that both transforming growth factor-beta 1 (TGF-β1) and tumour necrosis factor-alpha (TNF-α) down-regulate APA mRNA as well as protein expression in renal tubular epithelial cells and RCC cells in culture. In addition to this, both cytokines decrease dipeptidylpeptidase (DP) IV/CD26 mRNA, but not APN/CD13 mRNA expression. Otherwise, IL-4 and IL-13 increase CD13 as well as CD26 expression, but do not alter APA expression. Interferon-alpha (IFN-α), IFN-β and IFN-γ increase mRNA expression of all the three membrane ectopeptidases, whereas IL-1, IL-6, IL-7, IL-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been found to be without any significant effect. Treatment of cultured cells with cAMP-increasing agents, such as 8-bromo-cAMP or A23187, results in an increase in APA and DPIV/CD26, but no change in APN/CD13 mRNA expression or even a decrease in it. Furthermore, AP inhibitors can influence APA mRNA expression, since bestatin causes an increase in APA expression in a time- and dose-dependent manner, whereas bestatin does not change CD13 or CD26 expression. No difference could be found with respect to the modulation by different mediators between RCC cells and renal epithelial cells, though permanent tumour cell lines such as Caki-1 and Caki-2 may have lost some of the normally expressed peptidases.
Differential inhibitory effects of indomethacin, dexamethasone, and interferon-gamma (IFN-γ) on IL-11 production by rheumatoid synovial cells
Authors: Taki H , Sugiyama E , Mino T , Kuroda A , Kobayashi M 
Published: March 2003

SUMMARYIL-11, a member of the IL-6 type cytokines, has some biological activity related to the joint destruction in rheumatoid arthritis (RA), such as induction of osteoclast differentiation. However, its expression and regulation in rheumatoid inflamed joints has not been clarified. In the present study we examined the capacity of fresh rheumatoid synovial cells (fresh RSC) to produce IL-11, and the effect of indomethacin, dexamethasone and IFN-γ on IL-11 production. Fresh RSC obtained from eight patients with RA produced large amounts of IL-11, measured by ELISA, and showed strong expression of IL-11 mRNA, determined by Northern blotting. Indomethacin inhibited the production of IL-11 by about 55%. Prostaglandin E2 (PGE2) completely prevented the inhibition, suggesting that IL-11 production by fresh RSC was in part mediated by PGE2. Dexamethasone inhibited the production of IL-11 by more than 80%. Interestingly, the inhibition was not abolished by PGE2. IFN-γ inhibited the production of IL-11 from IL-1α-stimulated cultured rheumatoid synovial fibroblasts, although IFN-γ did not inhibit the production of IL-11 by fresh RSC. These results suggest that the production of IL-11 by rheumatoid synovia was differentially regulated by PGE2 and IFN-γ, and that treatment with indomethacin or dexamethasone decreased the level of IL-11 at inflammatory joints in patients with RA.