bluuebunny/crossref_metadata_2025_split huggingface dataset:
German cockroach extract increases bronchial epithelial cell interleukin‐8 expression
Authors: Bhat R. K. , Page K. , Tan A. , Hershenson M. B. 
Published: March 2003

SummaryBackground Cockroach exposure has been recognized as a common trigger for asthma. While dust mite and Aspergillus fumigatus aeroallergens have been noted to have direct effects on airway epithelium, direct effects of cockroach proteins have not been determined.Objective The purpose of this study was to investigate whether cockroach extract has a direct pro‐inflammatory effect on airway epithelium.Methods We examined the effect of crude German cockroach (Blattella germanica) extract on IL‐8 expression in a human bronchial epithelial cell line (16HBE14o‐cells) and primary human bronchial epithelial cells. Transcription from the IL‐8 promoter and protein abundance were determined by reporter assay and enzyme‐linked immunosorbent assay (ELISA), respectively. Endotoxin levels in the crude cockroach extracts were determined using the Limulus Amebocyte Lysate assay. Protease activity was assessed using Azocoll as a substrate.Results We found that crude cockroach extract induced a synergistic increase in TNF‐α‐induced transcription from the IL‐8 promoter. The synergistic effect was observed with as little as 0.3 µg/mL of crude cockroach extract, while larger concentrations (30 µg/mL) approximately doubled TNF‐α‐induced IL‐8 promoter activity. Similar effects of cockroach extract on IL‐8 protein abundance were observed in both 16HBE14o‐ and primary human bronchial epithelial cells. Addition of endotoxin at concentrations found in the cockroach extract had no effect on TNF‐α‐mediated IL‐8 expression. The serine protease inhibitors aprotinin and phenylmethylsulphonyl fluoride abolished cockroach‐induced synergy, while the cysteine protease inhibitors E64 and leupeptin had little effect. Measurement of protease activity using Azocoll as a substrate confirmed the presence of protease activity in cockroach extracts. Addition of recombinant Bla g 2, Bla g 3 and Bla g 5 had no effect on TNF‐α‐induced IL‐8 promoter activation. Finally, cockroach extract also increased TNF‐α‐induced transcription from the IL‐6 promoter.Conclusions German cockroach extract contains novel serine protease activity which has a direct pro‐inflammatory effect on airway epithelial cells
Is the increase in allergic respiratory disease caused by a cohort effect?
Authors: Linneberg A. , Nielsen N. H. , Madsen F. , Frølund L. , Dirksen A. , Jørgensen T. 
Published: March 2003

SummaryBackground Changes in lifestyle or environmental factors are responsible for the increasing prevalence of allergic respiratory disease. Establishing the time at which the increase began may provide a clue as to what factors possibly could have contributed to the increase. Many cross‐sectional studies have shown that the prevalence of allergic sensitization decreases with increasing age. This could reflect the natural course of allergic sensitization. Alternatively, this could reflect that the increase in sensitization is caused by a cohort effect, i.e. an increase among subjects born during recent decades.Objective The aim was to investigate age‐specific changes in the prevalence of allergic sensitization in a cohort of adults.Methods A total of 599 subjects aged 15 to 69 years participated in a cross‐sectional general population study in 1990. In 1998 they were invited to a follow‐up, and 64.4% (386/599) were re‐examined. Serum samples obtained from the participants in 1990 and 1998 were analysed for specific IgE to six common inhalant allergens with the same assay.Results The prevalence of allergic sensitization (specific IgE to at least one allergen) increased among subjects who were less than c. 30 years at baseline (1990), i.e. subjects born during the 1960s or later, while the prevalence was unchanged among subjects who were more than c. 30 years at baseline.Conclusions The results support the notion that the increasing prevalence of allergic respiratory disease is caused by a cohort effect. Thus, changes in lifestyle or environmental factors that occurred around or after 1960 may have contributed to this increase.
Constitutive secretion of the granule chymase mouse mast cell protease‐1 and the chemokine, CCL2, by mucosal mast cell homologues
Authors: Brown J. K. , Knight P. A. , Wright S. H. , Thornton E. M. , Miller H. R. P. 
Published: March 2003

SummaryBackground The mucosal mast cell (MMC) granule‐specific β‐chymase, mouse mast cell protease‐1 (mMCP‐1), is released systemically into the bloodstream early in nematode infection before parasite‐specific IgE responses develop and TGF‐β1 induces constitutive release of mMCP‐1 by homologues of MMC in vitro. Intraepithelial MMC may also express the chemokine CCL2 (monocyte chemotactic protein‐1) during nematode infection but the expression of this chemokine by MMC homologues has not been investigated.Objective To investigate the expression and to compare the mechanisms of constitutive release of the chymase, mMCP‐1, and the chemokine, CCL2.Methods MMC homologues were generated by culturing bone marrow cells in the presence of TGF‐β1, IL‐3, IL‐9 and stem cell factor (SCF). The intracellular distribution of mMCP‐1 and CCL2 was examined by confocal microscopy. The involvement of the Golgi complex and of protein synthesis in the constitutive release of mMCP‐1 and CCL2 was investigated using the Golgi‐disrupting agent brefeldin A and cycloheximide to block protein synthesis. Secreted analytes were quantified by ELISA.Results mMCP‐1 colocalized with Golgi matrix protein 130 but was most abundant in the granules, whereas CCL2 was not found in the granules but appeared to be located uniquely in the Golgi complex. Extracellular release of mMCP‐1 was significantly inhibited (≈ 40%) by cycloheximide and by the Golgi‐disrupting agent brefeldin A, indicating both continuous protein synthesis and transportation via the Golgi complex are required for optimal mMCP‐1 secretion. A similar but more marked inhibitory effect with both compounds was demonstrated on the constitutive secretion of CCL2.Conclusion The culture conditions that promote mMCP‐1 expression and release by MMC homologues also promote the expression and release of CCL2. Constitutive release involves de novo protein synthesis and requires a functional Golgi complex, suggesting that similar mechanisms of extracellular secretion operate for both mediators.
Immunoadjuvant properties of glove cornstarch powder in latex‐induced hypersensitivity
Authors: Barbara J. , Santais M.‐C. , Levy D. A. , Ruff F. , Leynadier F. 
Published: March 2003

SummaryBackground Cornstarch powder present in medical gloves plays an important role in latex‐induced hypersensitivity as allergen carrier either, by the inhalation route, by skin contact or by direct contact with mucous membranes.Objective Our objective was to test the hypothesis that cornstarch could act as an immunoadjuvant in immediate type‐I latex‐induced hypersensitivity.Methods Guinea‐pigs were sensitized by intraperitoneal route with two different antigens (latex proteins and ovalbumin) with or without cornstarch powder. Airway responsiveness after specific bronchial provocation was evaluated and specific IgG and IgG1 levels were determined by enzyme‐linked immunosorbant assay (ELISA). Controls were treated with cornstarch powder or saline alone.Results Animals sensitized with latex proteins (n = 7 in each group) showed significant bronchoconstriction (P < 0.03) and higher anti‐latex antibody levels than the controls (P < 0.005). Guinea‐pigs sensitized with latex‐contaminated cornstarch had higher levels of specific antibodies than those sensitized with latex alone (P < 0.05). Animals sensitized to latex mixed with cornstarch showed higher bronchospasm than those treated with latex alone (P < 0.003). Animals sensitized to ovalbumin mixed with cornstarch also showed higher antibody and bronchoconstriction levels (P < 0.05) than those immunized with ovalbumin alone but antibody titres were significantly lower than those of the animals treated with ovalbumin and Freund's complete adjuvant (P < 0.01; n = 5 in each group).Conclusion Our findings show that cornstarch powder increases antigen‐induced bronchoconstriction and antibody production. This role of immunoadjuvant is not antigen‐specific. The cornstarch powder used as donning agent in latex gloves is an allergen carrier and it can enhance latex‐induced hypersensitivity.
Elicitation of the allergic reaction in β‐lactoglobulin‐sensitized Balb/c mice: biochemical and clinical manifestations differ according to the structure of the allergen used for challenge
Authors: Adel‐Patient K. , Nahori M.‐A. , Proust B. , Lapa e Silva J. R. , Créminon C. , Wal J.‐M. , Vargaftig B. B. 
Published: March 2003

SummaryBackground Mouse models of allergy are used to study the mechanisms of induction and perpetuation of bronchopulmonary hyper‐reactivity (BHR) as related to eosinophils and specific IgE.Objective Our aim was to adapt the current model for the study of bovine β‐lactoglobulin (BLG), a major cow's milk allergen, and to further analyse the mechanisms of the acute and late allergic reaction.Methods Female Balb/c mice were sensitized intraperitoneally with BLG and the influence of the adjuvant and of the BLG dose on the IgE response was analysed, IgE and IgG1 epitopes being characterized. Once optimized, this model was applied to the study of the active phase of allergy in the respiratory tract after a single airway challenge using native or denatured BLG, which contains only linear epitopes.Results An immediate allergic reaction was characterized by the rapid release of histamine into the bronchoalveolar lavage fluids. Prostaglandin (PG)D2 was only present when the standard histamine‐releasing agent compound 48/80 or denatured BLG were used as triggers, whereas native BLG induced leukotriene release. Twenty‐four hours after challenge, BHR, eosinophil influx, IL‐4 and IL‐5 production, plasma exudation and mucus production were very much increased, differently depending on the allergen structure, and indicated the occurrence of the late allergic reaction. Our results show that the murine model can be used to study the mechanisms of allergy to clinically relevant antigens, such as those contained in cow's milk. The acute allergic reaction, which depends on the structural feature of the allergen, is composed of two distinct pathways characterized by peptido‐leukotrienes or PGD2 production, which may result from distinct activation intensities of mast cells, leading to distinct late reactions.Conclusion This study thus demonstrates a clear link between the structural feature of a protein, and the physiopathology of the experimental asthmatic reaction.
Psoriasis, psoriatic arthropathy and relapsing orbital myositis
Authors: Ajitsaria R. , Dale R. , Ferguson V. , Mayou S. , Cavanagh N. 
Published: March 2003

Abstract
Orbital myositis is an inflammatory disorder of the orbital muscles causing orbital pain and restriction of eye movements. Although rare in children, it is most frequently seen after orbital trauma or as a post-infectious process. We describe a child with chronic relapsing psoriasis, juvenile psoriatic arthritis and relapsing bilateral orbital myositis.
Early increase of CD4+ CD45RA+ and CD4+ CD95− cells with conserved repertoire induced by anti-retroviral therapy in HIV-infected patients
Authors: Silvestri G , Munoz-Calleja C , Bagnarelli P , Piedimonte G , Clementi M , Montroni M 
Published: March 2003

AbstractAdministration of anti-retroviral drugs induces a decrease of viral load associated with increase of CD4+ cell count in most HIV-infected patients. To investigate the early changes in CD4+ cell phenotype induced by anti-retroviral therapy, six patients with CD4+ cell count &gt; 100/mm3 and never treated with anti-HIV therapy were enrolled and blood samples collected several times within 14 days from the initiation of therapy with Zidovudine plus Didanosine. CD4+ cell count and HIV viraemia were investigated at each time point, as well as the expression of CD45RA, CD45RO and CD95/Fas molecules on CD4+ cells, and the T cell receptor (TCR) Vβ repertoire of CD4+ cells. All patients showed a rapid and dramatic decrease in viral load with a corresponding increase of CD4+ cell count. The main remodelling of CD4+ cell subpopulations took place in the first 14 days of therapy, and consisted of: (i) increased CD4+ CD45RA+/CD4+  CD45RO+ ratio; (ii) decrease of CD95/Fas expression. The rise in absolute number of CD4+ CD45RA+ cells was paralleled by an increase of CD4+ CD95/Fas− cells and accounted for most of the early increment of CD4+ cell count. The TCR Vβ repertoire of CD4+ cells was conserved after anti-HIV therapy, with the exception of two patients with expanded CD4+ Vβ12+ cells, which also tested CD45RA+ and CD95/Fas−. These experiments show that newcomer CD4+ lymphocytes are CD45RA+ CD95/Fas− cells, suggesting that blocking HIV replication causes an early and antigen-independent proliferation of possibly ‘naive’ cells unprimed for CD95/Fas-mediated apoptosis. These cells expressed a conserved and widespread TCR repertoire, suggesting that their capability for antigenic recognition is intact.
A study of the epitopes on steroid 21-hydroxylase recognized by autoantibodies in patients with or without Addison's disease
Authors: Volpato M , Prentice L , Chen D , Betterle C , Rees Smith B , Furmaniak J 
Published: March 2003

SUMMARYSteroid 21-hydroxylase (21-OH) autoantibodies are found in patients with autoimmune Addison's disease (AAD), either isolated or associated with autoimmune polyglandular syndrome (APS) type I and II and in adrenal-cortex autoantibody (ACA)-positive patients without AAD. In order to assess any differences in the 21-OH autoantibodies in these different patient groups, we have studied their reactivity with different epitopes on 21-OH using full length and modified 35S-labelled 21-OH proteins produced in an in vitro transcription/translation system. There were no major differences in the pattern of autoantibody reactivity with the different modified 21-OH proteins in patients with isolated AAD or with APS types I and II, and in 21-OH autoantibody-positive patients with clinical AAD, subclinical AAD and those maintaining a normal adrenal function. Our studies also indicate that the main epitopes for 21-OH autoantibodies in patients with different forms of autoimmune adrenal disease are located in the C-terminal end and in a central region of 21-OH.
Phenothiazine-induced increase in thyroid autoantigens and costimulatory molecules on thyroid cells: a pathophysiological mechanism for drug-induced autoimmunity?
Authors: Takorabet L , Ropars A , Stasiuk L , Raby C , Charreire J 
Published: March 2003

SUMMARYWe have previously demonstrated (J Immunol 1995; 154:3593) that MHC class II antigens can be induced on thyroid epithelial cells (TEC) by alimemazine, a member of the phenothiazine group. Although this expression of MHC class II antigens on TEC confers the theoretical ability to behave as antigen-presenting cells (APC), the simultaneous expression of self antigens and co-receptor(s) must also occur for efficient presentation of self antigens. Therefore, we investigated whether alimemazine applied at pharmacologic doses would modify the expression of thyroid antigens, and simultaneously, the expression of intercellular adhesion molecule-1 (ICAM-1), B7, and LFA-1 co-receptors in human TEC in culture. Using polymerase chain reaction (PCR) amplification and Northern blot analysis, we showed that alimemazine induces increases in thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) cDNA, within the first 2 h following its addition. This phenomenon is followed 48 h later by an increase of Tg and TSH-R protein expression on the surface of TEC. Furthermore, increases in the expression of ICAM-1 and B7 co-receptors were concomitantly observed. These results suggest that alimemazine, a drug currently used in paediatrics, could play a role in the induction and perpetuation of thyroid autoimmune disorders by transforming TEC into functional APC.
Tenidap decreases IL-8 and monocyte chemotactic peptide-1 (MCP-1) mRNA expression in the synovial tissue of rabbits with antigen arthritis and in cultured synovial cells
Authors: Palacios I , Lopez-Armada M J , Hernandez P , Sanchez-Pernaute O , Gutierrez S , Miguelez R , Martinez J , Egido J , Herrero-Beaumont G 
Published: March 2003

SUMMARYSince IL-8 and MCP-1 are chemoattractant proteins that participate in the recruitment of inflammatory cells into the arthritic joint, we examined the effects of tenidap, a new anti-inflammatory drug of the oxindole family, on IL-8 and MCP-1 expression in the joints of rabbits with acute antigen arthritis. The model was induced by injecting 5 mg/ml ovalbumin into the knees of 20 preimmunized rabbits. Animals were randomized into two groups: treated with tenidap (15 mg/kg per 12 h), or untreated. The effect of tenidap treatment was evaluated on chemokine production in synovial membranes of rabbits with arthritis and in cultured monocytic and synovial cells (SC). By immunoperoxidase staining, chemokines were localized in the synovial tissue. Chemokine messenger RNA levels in the synovial membranes and in cultured cells were analysed by reverse transcription-polymerase chain reaction (RT-PCR). At the end of the study, tenidap significantly reduced neutrophil infiltration into the joint cavity (27 ± 4 × 106 cells/ml versus 45 ± 6 × 106 cells/ml in untreated; P &lt; 0.05), and synovial effusion (134 ± 15 μl versus 236 ± 19 μl in untreated; P &lt; 0.005). Untreated rabbits showed synovial membrane up-regulation in mRNA expression of IL-8 and MCP-1 (11- and seven-fold versus healthy rabbits, respectively) that was markedly decreased by tenidap (two- and three-fold versus healthy rabbits, respectively). IL-8 and MCP-1 were localized in the synovial tissue in a perivascular pattern and areas of the interstitium and lining, mostly coinciding with cell infiltration. Tenidap also reduced the accumulation of IL-8 and MCP-1 proteins. In cultured synovial and monocytic cells, tumour necrosis factor-alpha (TNF-α) elicited an increase in gene expression of IL-8 (four- and nine-fold, respectively) and MCP-1 (nine- and four-fold, respectively) that was significantly reversed in both cell types by 10 μm tenidap. These results suggest that the beneficial effect of tenidap in acute antigen arthritis could be related to the down-regulation in gene expression and synthesis of IL-8 and MCP-1, two key chemokines involved in the recruitment of inflammatory cells.
Oxidative stress suppresses transcription factor activities in stimulated lymphocytes
Authors: Flescher E , Tripoli H , Salnikow K , Burns F J 
Published: March 2003

SUMMARYEffects of oxidative stress on stimulation-dependent signal transduction, leading to IL-2 expression, were studied. Purified quiescent human blood T lymphocytes were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure to hydrogen peroxide; and (iii) acute exposure to ionizing radiation. The cells were then stimulated for 6 h. DNA-binding activities (determined by the electrophoretic mobility shift assay) of three transcription factors: NFκB, AP-1 and NFAT, were abolished in the lymphocytes by all three modes of oxidative stress. The lymphocytes exhibited lipid peroxidation only upon exposure to the lowest level of hydrogen peroxide used (20 μm). All three modes of oxidative stress induced catalase activity in the lymphocytes. The only exception was hydrogen peroxide at 20 μm, which did not induce catalase activity. We conclude that: (i) suppression of specific transcription factor functions can potentially serve as a marker of exposure to oxidative stress and its effects on human lymphocytes; (ii) lipid peroxidation is only detectable in human lymphocytes upon exposure to weak oxidative stress which does not induce catalase activity; (iii) therefore, transcription factor DNA-binding activities are more sensitive to oxidative stress than lipid peroxidation.
Changes to the cytokine microenvironment in the genital tract mucosa of HIV+ women
Authors: Olaitan A , Johnson M A , Reid W M , Poulter L W 
Published: March 2003

SUMMARYAs previous studies have indicated that genital tract mucosal T cell function may be impaired in HIV infection, we investigated the T cell cytokine mRNA in the genital tract mucosa of HIV-infected women to determine if there are alterations in the cytokine profile which may explain the T cell impairment. The in situ hybridization technique was used to investigate the T helper-1 (Th1: IL-2, interferon-gamma (IFN-γ)) and Th2 cytokine (IL-4, IL-5, IL-10) mRNA profile in cervical biopsies from 10 HIV+ and 10 HIV− subjects. Cervical intraepithelial neoplasia (CIN) and genital infection had previously been excluded and the distribution of immunocompetent cells within the cervical mucosa was known for each subject. Non-parametric tests were used to compare the optical density (OD) of cytokine mRNA in the HIV+ and HIV− groups. Comparisons were also made between peripheral CD4 lymphocyte counts, cervical CD4/CD8 T lymphocyte ratios and cytokine mRNA OD in HIV+ subjects. The HIV+ women had significantly higher mRNA OD for the Th2 cytokines IL-4, IL-5 and IL-10 than HIV− women. There was also significantly lower IL-2 mRNA OD in the former group. HIV+ women had lower IFN-γ mRNA than HIV− women, but the difference was not statistically significant. There was no correlation between cytokine mRNA OD and peripheral CD4 count or cervical CD4/CD8 ratio. The predominance of Th2 cytokines, which are immuno-inhibitory, in the cervical mucosa of HIV+ women may underlie the impaired cytotoxic potential observed in the CD8+ T lymphocytes and may contribute to the susceptibility of HIV-infected women to recurrent genital tract infections and cervical neoplasia.
Binding of anticardiolipin antibodies to protein C via β2-glycoprotein I (β2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system
Authors: Atsumi T , Khamashta M A , Amengual O , Donohoe S , Mackie I , Ichikawa K , Koike T , Hughes G R V 
Published: March 2003

SUMMARYIt is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via β2-GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of β2-GPI by ELISA (anti-‘protein C’ antibody ELISA), and compared their binding with those obtained in the absence of β2-GPI. In the anti-‘protein C’ antibody ELISA system, 47% of 78 aPL+ patients had a positive titre in the presence of cardiolipin (CL) and β2-GPI, but binding was not found in the absence of β2-GPI. Highly significant correlations were found between the titre of anti-‘protein C’ antibody in the presence of β2-GPI and that of anti-β2-GPI antibody (r = 0·802, P = 0·0001). We further analysed the interaction between protein C, phospholipids, β2-GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of β2-GPI to protein C and its phospholipid dependency were investigated. β2-GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of β2-GPI (virtually anti-β2-GPI antibodies) was evaluated in the presence of cardiolipin and β2-GPI. All three human monoclonal aCL bound to protein C in the presence of CL and β2-GPI, whereas they did not in the absence of either β2-GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and β2-GPI, leading to protein C dysfunction.