bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytosine–phosphate–guanine motifs fail to promote T‐helper type 1‐polarized responses in human neonatal mononuclear cells
Authors: Prescott S. L. , Irwin S. , Taylor A. , Roper J. , Dunstan J. , Upham J. W. , Burgner D. , Richmond P. 
Published: March 2005

SummaryBackground
The T‐helper type 1 (Th1) trophic properties of bacterial cytosine–phosphate–guanine (CpG) motifs have made them logical adjuvants both for the suppression of Th2‐mediated allergic disease in early life and for promoting vaccine responses in neonates who have relatively immature Th1 function. However, little is known about their effects on immature immune responses in this period.Objectives
To compare the effects of CpG on adult and neonatal cellular immune responses to various stimuli.Methods
The immune responses of mononuclear cells (MC) derived from neonates (n=25) and their mothers (n=25) were compared in vitro. These were stimulated with house dust mite (HDM), CpG B, CpG C, non‐CpG oligodeoxynucleotides (ODN) or diphtheria toxoid (DT) in optimized conditions. In parallel cultures, CpGs were combined with HDM or DT antigens to assess the effect of the various ODN on these antigen‐specific responses. Lymphoproliferation and cytokine responses IL‐13, IFN‐γ, IL‐6, IL‐10, TNF‐α) were measured for all of the cultures described above.Results
Although neonates showed attenuated lymphoproliferation to CpG, the production of antigen‐presenting cell‐derived cytokines such as IL‐6 and IL‐10 and the up‐regulation of major histocompatibility complex class II (HLA‐DR) were detected at adult levels. T cell‐derived cytokines (IL‐13 and IFN‐γ) were not detectable in response to CpG alone. Most neonates also failed to produce detectable IFN‐γ to HDM or DT (unlike adults), but readily produced IL‐13 to these stimuli. The addition of CpG resulted in an increase in neonatal IFN‐γ production in response to HDM (P=0.011) and a similar but non‐significant trend with DT. However, rather than inhibiting Th2 IL‐13 responses, the addition of CpGs was associated with a significant increase in the IL‐13 responses to HDM (P=0.016) and DT (P=0.03), effects not seen in adults.Conclusions
This study provides further evidence that neonatal MC responses to CpG are functionally different from adults, and do not show clear Th1 polarization. The CpG associated increase in Th2 responses may reflect a potentiation of the normal neonatal Th2 propensity, or non‐specific activation of neonatal MC.
Polymorphisms in the 5‐lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population
Authors: Kedda M.‐A. , Worsley P. , Shi J. , Phelps S. , Duffy D. , Thompson P. J. 
Published: March 2005

SummaryBackground
The cysteinyl‐leukotrienes (cys‐LTs) are important pro‐inflammatory mediators in asthma, and have been shown to have a role in specific disease subtypes, including asthma severity. Few studies have investigated the role of polymorphisms in the ALOX5AP gene, encoding 5‐lipoxygenase activating protein (FLAP), and asthma. We hypothesized that polymorphisms in this gene are associated with asthma and in particular, with asthma severity, in an Australian population.Objective
To screen the coding region of the ALOX5AP gene for polymorphisms and to determine the association between previously described polymorphisms and asthma and asthma severity in an Australian population.Methods
We used PCR‐SSCP and PCR‐RFLP analysis to examine a previously described promoter polyA variable repeat polymorphism and two intronic polymorphisms (IVS2+12C>A, IVS2+105T>C), and to screen all five exons of the gene for new polymorphisms, in a large Australian population of randomly selected, non‐asthmatic controls (n=457), mild asthmatics (n=274), moderate asthmatics (n=231) and severe asthmatics (n=79).Results
We confirmed the presence of two polymorphisms in intron 2 and found no association between these polymorphisms and asthma or asthma severity, nor between a promoter polymorphism in the ALOX5AP gene and asthma or asthma severity. Gene fragment analysis of the promoter polymorphism revealed novel, conserved repeat numbers in our population, and no new polymorphisms were found in the coding region of the gene.Conclusion
These findings in a large, well characterized asthma population, reveal that, while FLAP is an important enzyme in cys‐LTs biosynthesis, polymorphisms in the ALOX5AP gene are not likely to be functionally associated with the asthma phenotype.
A polymorphism in the promoter region of the human interleukin‐16 gene is not associated with asthma or atopy in an Australian population
Authors: Akesson L. S. , Duffy D. L. , Phelps S. C. , Thompson P. J. , Kedda M.‐A. 
Published: March 2005

SummaryBackground
IL‐16 is an immunomodulatory cytokine whose expression is increased in the bronchial mucosa, bronchoalveolar lavage fluid and induced sputum of asthmatic patients. It has been suggested that IL‐16 has a regulatory role in the pathophysiology of asthma. A single‐nucleotide polymorphism (T−295C) has been described in the promoter region of the gene and it has been hypothesized that this polymorphism may be associated with altered levels of IL‐16 expression, and account for the increased levels of IL‐16 seen in the asthmatic airway.Objective
To determine the association between the T−295C promoter polymorphism and asthma, disease severity and atopy in a large Australian Caucasian population.Methods
We used PCR and restriction fragment length polymorphism analysis to establish the allele frequency of the T−295C promoter polymorphism in a random Australian Caucasian population (n=176) and to characterize the polymorphism in a large Australian Caucasian population of mild (n=273), moderate (n=230) and severe (n=77) asthmatic patients, and non‐asthmatic controls (n=455). Genotype association analyses were performed using χ2 tests.Results
The polymorphic C allele was present in 19% of the asthmatic population and 21% of the non‐asthmatic population. There was no association between the polymorphism and asthma (P=0.153) nor with asthma severity (P=0.417) or atopy (P=0.157) in this population.Conclusion
Although it has been hypothesized that the T−295C promoter polymorphism may be associated with increased IL‐16 gene expression, it is not associated with asthma, disease severity or atopy in this Australian population.
Percutaneous application of peptidoglycan from Staphylococcus aureus induces an increase in mast cell numbers in the dermis of mice
Authors: Matsui K. , Nishikawa A. 
Published: March 2005

SummaryBackground
Atopic dermatitis (AD) is a chronic inflammatory skin disease with immunopathologic features that vary depending on the duration of the lesion. The dermis of lesional skin of AD patients shows an increased number of inflammatory cells such as mast cells, eosinophils and mononuclear cells and superficial Staphylococcus aureus colonization.Objective
The purpose of this study was to determine the effects of peptidoglycan (PEG) from S. aureus on mast cell induction in murine skin.Methods
PEG was applied to barrier‐disrupted abdominal skin of mice every 5 days and the number of mast cells in the abdominal skin was counted 20 days after the first application. The cytokine response was investigated by RT‐PCR and immunohistologic analysis.Results
The number of mast cells in the skin of mice treated with PEG was increased significantly compared with that of mice given phosphate‐buffered saline. In addition, application of PEG to the abdominal skin increased the expression of mRNA for transforming growth factor‐β1 (TGF‐β1), which supports mast cell migration, but not that for IL‐3 or stem cell factor, which support both mast cell proliferation and mast cell migration. Immunohistologic analysis demonstrated that levels of TGF‐β1 transcripts corresponded with those of protein synthesis in the epidermis. TGF‐β1 was found to be highly expressed in keratinocytes of the basal epidermis of PEG‐treated skin. Furthermore, intraperitoneal injection of anti‐TGF‐β1 antibodies neutralized the induction of mast cells into the skin.Conclusion
These results suggest that PEG may have the ability to induce an increase in mast cell numbers in the skin through TGF‐β1 production by epidermal keratinocytes. Skin inflammation might therefore be linked to colonization with S. aureus in AD patients.
Why generic and disease‐specific quality‐of‐life instruments should be used together for the evaluation of patients with persistent allergic rhinitis
Authors: Leong K. P. , L. Yeak S. C. , M. Saurajen A. S. , H. Mok P. K. , Earnest A. , Siow J. K. , C. Chee N. W. , Yeo S. B. , Khoo M. L. , Y. Lee J. C. , Seshadri R. , Chan S. P. , Tang C. Y. , Chng H. H. 
Published: March 2005

SummaryBackground
The importance of assessing health‐related quality of life (HRQL) of patients with allergic rhinitis (AR) has been well established, but the specific roles of rhinitis‐specific or general health instruments have not been delineated.Objective
We analysed the psychometric properties of a disease‐specific instrument, the Rhinoconjunctivitis Quality‐of‐Life Questionnaire (RQLQ) and the general health instrument, the Medical Outcome Short‐Form 36 (SF‐36) as they are employed in combination in patients with persistent AR in clinical practice.MethodWe analysed the data collected from a prospective study of 43 newly diagnosed patients with persistent AR and 44 controls. We interviewed the patients four times, at baseline, weeks 4, 8 and 10.Results
The RQLQ and SF‐36 have good discriminative property, internal consistency, and test–retest reliability. The RQLQ is superior to the SF‐36 as an evaluative instrument because more of its domains respond to change, the magnitude of change was greater, and the response was faster. The SF‐36 is more susceptible to floor and ceiling effects. Both instruments are unsuitable for mildly symptomatic patients based on Rasch model analysis. Each questionnaire assesses a distinct and significant portion of the total HRQL of persistent AR.Conclusion
The SF‐36 and RQLQ are good for discriminating rhinitis patients from controls, but the former is poor for detecting changes in QOL. Both are inappropriate for mildly symptomatic patients. Each instrument measures non‐overlapping halves of the measurable HRQL. For an assessment of the HRQL in persistent AR that is complete and responsive both instruments should be employed together.
Transforming growth factor‐β1 increases CXCR4 expression, stromal‐derived factor‐1α‐stimulated signalling and human immunodeficiency virus‐1 entry in human monocyte‐derived macrophages
Authors: Chen Shuzhen , Tuttle Daniel L. , Oshier Joseph T. , Knot Harm J. , Streit Wolfgang J. , Goodenow Maureen M. , Harrison Jeffrey K. 
Published: March 2005

SummaryStromal‐derived factor‐1 (SDF‐1/CXCL12) and its receptor CXCR4 play crucial roles in leukocyte migration and activation, as well as embryogenesis, angiogenesis, cancer and viral pathogenesis. CXCR4 is one of the major human immunodeficiency virus‐1 (HIV‐1) coreceptors on macrophages. In many tissues macrophages are one of the predominant cell types infected by HIV‐1 and act as a reservoir for persistent infection and viral dissemination. In patients infected by HIV‐1, blood and tissue levels of transforming growth factor‐β1 (TGF‐β1) are increased. The purpose of this study was to evaluate the effects of TGF‐β1 on CXCR4 expression and function in primary human monocyte‐derived macrophages (MDMs) and rat microglia. TGF‐β1 up‐regulated CXCR4 and enhanced SDF‐1α‐stimulated ERK1,2 phosphorylation in these cells. The increased CXCR4 expression in human MDMs resulted in increased susceptibility of the cells to entry by dual‐tropic CXCR4‐using HIV‐1 (D‐X4). In contrast, TGF‐β1 failed to increase CCR5 expression or infection by a CCR5‐using virus in MDMs. Our data demonstrate that TGF‐β1 enhances macrophage responsiveness to SDF‐1α stimulation and susceptibility to HIV‐1 by selectively increasing expression of CXCR4. The results suggest that increased expression of CXCR4 on macrophages may contribute to the emergence of dual‐tropic X4 viral variants at later stages of HIV‐1 infection.
Heat shock up‐regulates expression of Toll‐like receptor‐2 and Toll‐like receptor‐4 in human monocytes via p38 kinase signal pathway
Authors: Zhou Jun , An Huazhang , Xu Hongmei , Liu Shuxun , Cao Xuetao 
Published: March 2005

SummaryHeat stress can alert innate immunity by inducing stress proteins such as heat‐shock proteins (HSPs). However, it remains unclear whether heat stress affects the activation of antigen‐presenting cell (APC) in response to pathogen‐associated molecule patterns (PAMPs) by directly regulating pathogen recognition receptors (PRRs). As an important kind of PRRs, Toll‐like receptors (TLRs) play critical roles in the activation of immune system. In this study, we demonstrated that heat shock up‐regulated the expression of HSP70 as well as TLR2 and TLR4 in monocytes. The induction of TLRs was prior to that of HSP70, which suggesting the up‐regulation of TLR2 and TLR4 might be independent of the induction of HSP70. Heat shock activated p38 kinase, extracellular signal‐related kinase (ERK) and nuclear factor‐kappa B (NF‐κB) signal pathways in monocytes. Pretreatment with specific inhibitor of p38 kinase, but not those of ERK and NF‐κB, inhibited heat shock‐induced up‐regulation of TLR2 and TLR4. This indicates that p38 pathway takes part in heat shock‐induced up‐regulation of TLR2 and TLR4. Heat shock also increased lipoteichoic acid‐ or lipopolysaccharide‐induced interleukin‐6 production by monocytes. These results suggest that the p38 kinase‐mediated up‐regulation of TLR2 and TLR4 might be involved in the enhanced response to PAMP in human monocytes induced by heat shock.
Complement receptors regulate lipopolysaccharide‐induced T‐cell stimulation
Authors: Kaya Ziya , Tretter Theresa , Schlichting Jens , Leuschner Florian , Afanasyeva Marina , Katus Hugo A. , Rose Noel R. 
Published: March 2005

SummaryComplement receptors type 1 and 2 (CR1 (CD35)/CR2 (CD21)) are known to enhance the adaptive immune response. In mice, CR1/CR2 are expressed on B cells, follicular dendritic cells, and activated granulocytes. Recently, we showed that a subset of CD44high and CD62Llow T cells also expresses CR1 and CR2. We now report that CR1/CR2 are detectable on both CD4+ and CD8+ subsets of T cells. Lipopolysaccharide (LPS) from Gram‐negative bacteria causes polyclonal activation of B cells and stimulation of macrophages and other antigen‐presenting cells. We further demonstrate that LPS induced marked up‐regulation of CD25 and CD69 on T cells from CR1/CR2 sufficient (Cr+/+), but significantly lower up‐regulation on T cells from CR1/CR2 deficient (Cr–/–) mice. These findings point to a novel mechanism by which CR1/CR2 modulates the activation of T cells by LPS.
T‐cell homeostasis in mice exposed to airborne xenobiotics
Authors: Drela Nadzieja , Bień Justyna , Kozłowska Ewa 
Published: March 2005

SummaryMany effects of environmental toxic agents contribute to the deregulation of immune system homeostasis. Here we demonstrate that the effect of airborne suspended matter (ASM) on the generation of mouse T cells is reversible. This reversal can be achieved by an active process that returns the T cells to homeostasis and does not result from the simple effect of ASM deprivation. An accelerated development of thymocytes and increased influx of T‐cell progenitors to the thymus in mice exposed to environmental xenobiotics has been postulated. This hypothesis has been confirmed by parallel increases in the percentages of single‐positive and triple‐negative thymocytes. Enhanced expression of thymocyte surface markers related to positive selection has also been observed. The pathway of T‐cell progenitor development is favoured in the bone marrow of mice exposed to ASM.
B‐cell reconstitution by transplantation of B220+ CD117+ B‐lymphoid progenitors into irradiated mice
Authors: Kawaguchi Susumu 
Published: March 2005

SummaryBone marrow cells of 4‐week‐old CBA/J mice were searched for progenitors that can reconstitute CBA‐type B lineage (B220+) cells after transplantation into irradiated (BALB/c × CBA/J) F1 mice. In recipients of B lineage‐committed B220+ CD117+ cells, which were CD19+ CD127+ CD25– IgM–, numbers of CBA‐type B220+ cells had increased greatly by day 8 after transplantation. This increase stopped by day 10 but cell numbers remained at this level for at least 8 weeks. B‐cell production in the bone marrow of B220+ CD117+ cell recipients occurred even 8 weeks after transplantation. Probably, the transplanted B‐lymphoid progenitors are capable of self‐renewing up to 8 weeks after transplantation. B lineage‐ uncommitted CD117high CD71– cells, which were B220– and included haematopoietic stem cells, could also reconstitute B lineage bone marrow cells after transplantation. Sequential development of CD117+, CD25+ and IgM+ cells in CBA‐type B220+ bone marrow cells occurred 2–4 days faster in recipients of B220+ CD117+ progenitors than in recipients of CD117high CD71– progenitors, suggesting that the development of the former progenitors from the latter may take 2–4 days.
Transforming growth factor‐β1 enhances the interferon‐γ‐dependent, interleukin‐12‐independent pathway of T helper 1 cell differentiation
Authors: Smeltz Ronald B. , Chen June , Shevach Ethan M. 
Published: March 2005

SummaryTransforming growth factor (TGF)‐β, a pleiotropic cytokine that has multiple effects on immune responses, has been shown to inhibit interleukin (IL)‐4/GATA‐3 expression as well as T helper 2 (Th2) differentiation. Consistent with these reports, we found that priming T cells from DO11.10 transgenic mice with antigen in the presence of TGF‐β inhibited GATA‐3 expression and the development of IL‐4‐producing T cells. Unexpectedly, the inhibition of Th2 development was accompanied by a substantial increase in the number of interferon‐γ (IFN‐γ)‐producing cells. T cells primed with TGF‐β secreted IFN‐γ in response to both T‐cell receptor ligation and IL‐12/IL‐18 stimulation, and expressed high levels of T‐bet and low levels of GATA‐3. The TGF‐β‐mediated enhancement of T helper 1 (Th1) priming was independent of IL‐12 and signal transducer and activator of transcription (STAT)‐4, but required endogenous IFN‐γ. TGF‐β‐mediated enhancement of the IFN‐γ‐dependent, IL‐12‐independent pathway of Th1 priming was mediated primarily by the inhibition of IL‐4 produced by memory/activated T cells in the unfractionated CD4+ responder population. Nevertheless, TGF‐β did not inhibit this pathway of Th1 differentiation when purified naive CD4+ T cells were used as responders. These data have important implications for strategies being considered for the use of TGF‐β‐producing T cells for the treatment of autoimmune disorders.
Expression and activity of multidrug resistance protein 1 in a murine thymoma cell line
Authors: Echevarria‐Lima Juliana , Kyle‐Cezar Fernanda , P. Leite Daniela F. , Capella Luiz , Capella Márcia A. M. , Rumjanek Vivian M. 
Published: March 2005

SummaryMultidrug resistance proteins [MRPs and P‐glycoprotein (Pgp)] are members of the family of ATP‐binding cassette (ABC) transport proteins, originally described as being involved in the resistance against anti‐cancer agents in tumour cells. These proteins act as ATP‐dependent efflux pumps and have now been described in normal cells where they exert physiological roles. The aim of this work was to investigate the expression and activity of MRP and Pgp in the thymoma cell line, EL4. It was observed that EL4 cells expressed mRNA for MRP1, but not for MRP2, MRP3 or Pgp. The activity of ABC transport proteins was evaluated by using the efflux of the fluorescent probes carboxy‐2′‐7′‐dichlorofluorescein diacetate (CFDA) and rhodamine 123 (Rho 123). EL4 cells did not retain CFDA intracellularly, and MRP inhibitors (probenecid, indomethacin and MK 571) decreased MRP1 activity in a concentration‐dependent manner. As expected, EL4 cells accumulated Rho 123, and the presence of cyclosporin A and verapamil did not modify this accumulation. Most importantly, when EL4 cells were incubated in the presence of the MRP1 inhibitors indomethacin and MK 571 for 6 days, they started to express CD4 and CD8 molecules on their surface, producing double‐positive cells and CD8 single‐positive cells. Our results suggest that MRP activity is important for the maintenance of the undifferentiated state in this cell type. This finding might have implications in the physiological process of normal thymocyte maturation.
Bodyguards and assassins: Bcl‐2 family proteins and apoptosis control in chronic lymphocytic leukaemia
Authors: Packham Graham , Stevenson Freda K. 
Published: March 2005

SummaryChronic lymphocytic leukaemia (CLL) is the most common B‐cell malignancy in the Western world and exists as subtypes with very different clinical courses. CLL is generally described as a disease of failed apoptosis. Apoptosis resistance may stem from a combination of microenvironmental survival signals as well as from intrinsic alterations in the apoptotic machinery within the CLL cell. The molecular mechanism involved in controlling apoptosis in CLL is complex and is influenced by many factors, including Bcl‐2 family proteins, which are critical regulators of cell death. Here we review the significance of apoptosis dysregulation in CLL, focusing on the role of Bcl‐2 and related Bcl‐2 family proteins, such as Bax and Mcl‐1. The differential properties of the newly described subsets of CLL are also highlighted.
Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin‐12/interleukin‐23‐deficient mice
Authors: Bastos Karina R. B. , De Deus Vieira de Moraes Luciana , Zago Cláudia A. , Marinho Cláudio R. F. , Russo Momtchilo , Alvarez José M. M. , D'Império Lima Maria R. 
Published: March 2005

SummaryWe have previously shown that macrophages from interleukin (IL)‐12p40 gene knockout (IL‐12/IL‐23–/–) mice have a bias towards the M2 activation profile, spontaneously secreting large quantities of transforming growth factor‐β1 (TGF‐β1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ). To verify whether the activation profile of dendritic cells (DCs) is also influenced by the absence of IL‐12/IL‐23, bone marrow‐derived DCs from IL‐12/IL‐23–/– and C57BL/6 mice were evaluated. At first we noticed that ≈ 50% of the C57BL/6 DCs were dead after LPS‐induced maturation, whereas the mortality of IL‐12/IL‐23–/– DCs was < 10%, a protective effect that diminished when recombinant IL‐12 (rIL‐12) was added during maturation. Similarly to macrophages, mature IL‐12/IL‐23–/– DCs (mDCs) produced higher levels of TGF‐β1 and lower levels of NO than C57BL/6 mDCs. NO release was IFN‐γ‐dependent, as evidenced by the poor response of IFN‐γ–/– and IL‐12/IL‐23–/–IFN‐γ–/– mDCs. Nevertheless, IFN‐γ deficiency was not the sole reason for the weak NO response observed in the absence of IL‐12/IL‐23. The high level of TGF‐β1 secretion by IL‐12/IL‐23–/– mDCs could explain why exogenous IFN‐γ partially restored the NO production of IFN‐γ–/– mDCs, while IL‐12/IL‐23–/– IFN‐γ–/– mDCs remained unresponsive. We also showed that CD4+ T‐cell proliferation was inhibited by C57BL/6 mDCs, but not by IL‐12/IL‐23–/– mDCs. IFN‐γ and NO appear to mediate this antiproliferative effect because this effect was not observed in the presence of mDCs from IFN‐γ–/– or IL‐12/IL‐23–/– IFN‐γ–/– mice and it was attenuated by aminoguanidine. We conclude that the presence of IL‐12/IL‐23 during LPS‐induced maturation influences the activation profile of DCs by a mechanism that is, only in part, IFN‐γ dependent.