bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Concentrations of Interleukin 1ß, CXCL10, and Interferon-γ in Mixed Cryoglobulinemia Associated with Hepatitis C Infection
Authors: ANTONELLI ALESSANDRO , FERRI CLODOVEO , FERRARI SILVIA MARTINA , GHIRI EMILIANO , MARCHI SANTINO , SEBASTIANI MARCO , FALLAHI POUPAK 
Published: November 2009

Objective.Mixed cryoglobulinemia (MC) is a systemic vasculitis of small and medium-size vessels, often associated with the hepatitis C virus. Research has shown an emerging role for chemokines and type 1 cytokines in the pathophysiology of this vasculitis. Interleukin 1 (IL-1) plays a role in initiating the cascade of immunoinflammatory responses, and levels of the interferon-γ (IFN-γ) inducible chemokine CXCL10 have been shown to be significantly associated with the presence of active vasculitis in patients with MC. We evaluated serum levels of IL-1ß, IFN-γ, and CXCL10 in a series of patients with hepatitis C-related MC (MC+HCV), and correlated these measurements with clinical disease features.Methods.Serum IL-1ß, IFN-γ, and CXCL10 were assayed in 54 patients with MC+HCV, in 54 sex- and age-matched patients with type C chronic hepatitis without cryoglobulinemia (HCV+), and in 54 controls.Results.MC+HCV patients showed significantly higher mean IL-1ß and CXCL10 serum levels than controls (p < 0.01) or HCV+ patients (p < 0.01). CXCL10 was significantly increased in 14 cryoglobulinemic patients with active vasculitis (necrotizing vasculitis or vasculitic skin ulcers) compared to those without (p < 0.001); IL-1ß was increased in cryoglobulinemic patients with active vasculitis (p = 0.06). No differences were observed for serum IFN-γ levels.Conclusion.Serum levels of IL-1ß and CXCL10 were high in patients with MC+HCV. Increased CXCL10 and IL-1ß levels were associated with the presence of active vasculitis in MC+HCV patients.
Baseline Glucocorticoid Dose and Bone Mineral Density Response with Teriparatide or Alendronate Therapy in Patients with Glucocorticoid-induced Osteoporosis
Authors: DEVOGELAER JEAN-PIERRE , ADLER ROBERT A. , RECKNOR CHRIS , SEE KYOUNGAH , WARNER MARGARET R. , WONG MAYME , KROHN KELLY 
Published: November 2009

Objective.This post-hoc analysis studied the effect of baseline glucocorticoid dose on the 18-month bone mineral density (BMD) response to teriparatide 20μg/day or alendronate 10 mg/day in 387 patients with glucocorticoid-induced osteoporosis (GIO) from a randomized, double-blind trial.Methods.Lumbar spine (LS), femoral neck (FN), and total hip (TH) BMD were measured at baseline and 18 months. Mean baseline glucocorticoid dose was categorized as low (≤ 5 mg/day), medium (> 5 and < 15 mg/day), or high (≥ 15 mg/day).Results.Baseline LS, FN, and TH BMD were similar between groups, and between glucocorticoid dose categories within each group. LS BMD increases at the low, medium, and high glucocorticoid doses were 8.1%, 6.6%, and 4.6%, respectively, with teriparatide, and 3.6%, 2.8%, and 2.3% with alendronate. Analyzed as a continuous variable, higher glucocorticoid doses had a negative, but non-significant, effect on the percentage increase in LS BMD in both groups. Glucocorticoid dose did not significantly affect FN or TH BMD increases in either group. Across the 3 glucocorticoid dose categories, the overall LS BMD increases were different for both treatments combined (p = 0.033), but the relative differences between the treatment groups were not different (interaction, p = 0.52).Conclusion.Teriparatide and alendronate increased LS and hip BMD across a range of baseline glucocorticoid doses. LS BMD increases with teriparatide were greater in the low-dose category than in the high-dose category. Overall LS BMD increases were significantly greater with teriparatide compared with alendronate, which may reflect the respective anabolic and antiresorptive mechanisms of action. Clinical Trial Registry Number: NCT00051558.
Heterogeneity Within the Fibromyalgia Population: Theoretical Implications of Variable Tender Point Severity Ratings
Authors: WILSON HILARY D. , STARZ TERENCE W. , ROBINSON JAMES P. , TURK DENNIS C. 
Published: November 2009

Objective.The American College of Rheumatology (ACR) tender point (TP) criterion is used in diagnosing fibromyalgia syndrome (FM). There has been little research investigating patterns of positive TP. We investigated response patterns of TP in a sample of patients with FM.Methods.Manual TP survey data were available on 1433 patients with FM. Factor analysis was conducted on ACR TP and control (CON) points. Factor scores were cluster analyzed to identify subgroups based on TP scores. Subgroups were compared on demographic and psychosocial variables.Results.Factor analysis resulted in 4 TP groupings: neck/shoulder girdle, gluteal/trochanteric, and upper extremity regions, and a set of CON TP. Cluster analysis revealed 3 clusters. Group 1 was high on all 3 TP regions and the CON set; Group 2 moderate on the 3 TP regions, low on the CON set; and Group 3 was relatively low on all 3 TP regions and the CON set. The group highest on the CON and TP regions reported the greatest pain (7.58 ± 1.23; p < 0.001), sleep disturbance (7.05 ± 1.61; p < 0.001), anxiety (10.14 ± 4.57; p < 0.001), and depression (8.42 ± 4.4; p < 0.001).Conclusion.TP severity ratings varied among cluster groups, suggesting patients with FM are not homogeneous. Variations in TP severity provide information regarding the degree to which FM affects patients’ quality of life. Patients with elevated scores on the CON TP demonstrated a general pattern reflecting lower thresholds for symptom reporting and, perhaps, disease severity. Research is needed to elucidate mechanisms underlying heterogeneity among the FM population.
Monitoring Methotrexate Toxicity in Juvenile Idiopathic Arthritis
Authors: KOCHARLA LAKSHMI , TAYLOR JANALEE , WEILER TRACEY , TING TRACY V. , LUGGEN MICHAEL , BRUNNER HERMINE I. 
Published: November 2009

Objective.To determine the frequency of laboratory abnormalities with methotrexate (MTX) use in patients with juvenile idiopathic arthritis (JIA); to identify potential risk factors for MTX toxicity requiring medical interventions; and to compare the frequency of liver function abnormalities in patients treated with MTX to those not treated with MTX.Methods.Results of MTX surveillance laboratory testing (SLT) available in clinical databases were reviewed for 588 children with JIA. Information on demographics, JIA features, and factors previously associated with increased frequency of SLT abnormalities was obtained.Results.Results of SLT performed in at least 4-month intervals were available for 138 JIA patients whose JIA was not treated with MTX, and for 198 JIA patients treated with MTX plus folic acid. On SLT of the MTX-treated patients, there were 44 of 2650 (1.7%) AST tests and 90 of 2647 (3.4%) ALT tests that exceeded 2 times the upper limit of normal (> 2 ULN) in 30 children (15%). AST or ALT tests at > 2 ULN occurred more often with systemic JIA (p = 0.04), macrophage activation syndrome, during infections, in systemic antibiotic use, and after intensifying JIA drug regimens. AST or ALT results at > 2 ULN were as frequent among MTX-treated children as those not treated with MTX. Renal and hematological abnormalities with MTX were uncommon.Conclusion.Liver enzyme abnormalities > 2 ULN are rare in JIA, irrespective of MTX exposure. These data suggest that the adult standard of SLT every 4–8 weeks may not be necessary in children treated with MTX, especially if certain risk factors are absent.
Calcium-Independent Phospholipase A2β-Akt Signaling Is Involved in Lipopolysaccharide-Induced NADPH Oxidase 1 Expression and Foam Cell Formation
Authors: Lee Sun-Hye , Park Dae-Weon , Park Sung Chul , Park Yun-Ki , Hong Seong Yeon , Kim Jae-Ryong , Lee Chu-Hee , Baek Suk-Hwan 
Published: November 2009

Abstract
Foam cell formation is the most important process in atherosclerosis, and low density lipoprotein oxidation by reactive oxygen species (ROS) is the key step in the conversion of macrophages to foam cells. This study reveals the control mechanism of the gene for NADPH oxidase 1 (Nox1), which produces ROS in the formation of foam cells by stimulating TLR4. Treatment of macrophages by the TLR4 agonist LPS stimulated ROS production and ROS-mediated macrophage to foam cell conversion. This LPS-induced ROS production and foam cell formation could be abrogated by pretreatment of macrophages with N-acetyl cysteine or apocynin. LPS increased Nox1 promoter activity, and resultant expression of mRNA and protein. Small interfering RNA mediated inhibition of Nox1 expression decreased LPS-induced ROS production and foam cell formation. LPS-mediated Nox1 expression and the responses occurred in a calcium-independent phospholipase A2 (iPLA2)-dependent manner. The iPLA2β-specific inhibitor S-BEL or iPLA2β small interfering RNA attenuated LPS-induced Nox1 expression, ROS production, and foam cell formation. In addition, activation of iPLA2β by LPS caused Akt phosphorylation and was followed by increased Nox1 expression. These results suggest that the binding of LPS and TLR4 increases Nox1 expression through the iPLA2β-Akt signaling pathway, and control ROS production and foam cell formation.
Deciphering the Immune Function and Regulation by a TLR of the Cytokine EMAPII in the Lesioned Central Nervous System Using a Leech Model
Authors: Schikorski David , Cuvillier-Hot Virginie , Boidin-Wichlacz Céline , Slomianny Christian , Salzet Michel , Tasiemski Aurélie 
Published: November 2009

Abstract
A highly conserved ortholog of the human complex p43/endothelial monocyte-activating polypeptide II (EMAPII) was characterized in the CNS of the leech Hirudo medicinalis. As observed in mammals, the leech complex is processed to release the cytokine HmEMAPII. Taking advantages of these similarities, we have attempted to elucidate the role of EMAPII in the CNS using the leech model. Although EMAPII is considered a modulator of inflammatory reactions within the peripheral innate immune response in humans, its function in CNS immunity has yet to be described. Chemotaxis assays were conducted, revealing the ability of EMAPII to exert a chemoattractant effect on both leech and human microglial cells, indicating a novel function of this cytokine in the human brain. Quantitative RT-PCR analysis together with in situ hybridization and immunohistochemistry approaches showed that bacterial challenge induced the expression of HmEMAPII at the lesion site where microglial cells accumulated. Moreover, gene silencing experiments have demonstrated that the gene expression of HmEMAPII is under the control of a signaling pathway associated with the TLR HmTLR1, newly characterized in the CNS of our model. To the best of our knowledge, this is the first report showing evidence for (1) the chemoattractant properties of EMAPII on leech and human microglial cells, (2) the regulation by a TLR of the expression of a gene encoding a cytokine in the CNS of an invertebrate, and (3) an immune function of a TLR in a lophotrochozoan model.
Apoptotic Dendritic Cells Induce Tolerance in Mice through Suppression of Dendritic Cell Maturation and Induction of Antigen-Specific Regulatory T Cells
Authors: Kushwah Rahul , Oliver Jordan R. , Zhang Jinyi , Siminovitch Katherine A. , Hu Jim 
Published: November 2009

Abstract
Dendritic cell (DC) apoptosis has been shown to play a role in maintaining a balance between tolerance and immunity. However, the mechanisms of how DC apoptosis affects the immune response are unclear. We have shown that in vitro culture of apoptotic DCs with immature DCs, results in their uptake by immature DCs, which subsequently turn into tolerogenic DCs, which then secrete TGF-β1 and induce Foxp3+ regulatory T cells (Tregs). In this study we looked at the effects of apoptotic DCs in vivo. Here we show that apoptotic DCs are taken up by viable DCs in vivo, which suppresses the ability of viable DCs to undergo maturation and subsequent migration to the lymph nodes in response to LPS. Additionally, delivery of apoptotic DCs to LPS inflamed lungs results in resolution of inflammation, which is mediated by the ability of apoptotic DCs to suppress response of viable DCs to LPS. Additionally, apoptotic DCs also induce TGF-β1 secretion in the mediastinal lymph nodes, which results in expansion of Foxp3+ Tregs. Most importantly, we show that delivery of apoptotic DCs followed by OVA in CFA to mice suppresses T cell response to OVA and instead induces de novo generation of OVA-specific Tregs. Furthermore, delivery of apoptotic DCs followed by OVA in CFA results in expansion of Tregs in TCR transgenic (OT-II) mice. These findings demonstrate that apoptotic DCs are taken up by viable DCs in vivo, which promotes tolerance through suppression of DC maturation and induction of Tregs.
Dendritic Cells Matured by Inflammation Induce CD86-Dependent Priming of Naive CD8+ T Cells in the Absence of Their Cognate Peptide Antigen
Authors: Maroof Asher , Beattie Lynette , Kirby Alun , Coles Mark , Kaye Paul M. 
Published: November 2009

Abstract
Dendritic cells (DC) licensed by the interaction between pathogen products and pattern recognition receptors can activate naive T cells to undergo Ag-dependent proliferation and cytokine production. In contrast, DC induced to mature by trans-acting inflammatory stimuli are believed to only be capable of supporting Ag-dependent proliferative responses. In this study, we show that uninfected DC matured as a consequence of Leishmania-induced inflammation induce CD8+ T cells to proliferate in the absence of their cognate Ag. We separated splenic DC from Leishmania donovani-infected mice into those that contained parasites and had been activated to induce IL-12p40, from those that had undergone only partial maturation, measured by increased CD86 expression in the absence of IL-12p40 induction. We then showed that these partially matured DC could induce exogenous peptide-independent proliferation of OT-I and F5 CD8+ TCR transgenic T cells, as well as polyclonal CD8+ T cells. Proliferation of OT-I cells was significantly inhibited in vitro and in vivo by anti-CD86 mAb but not by anti-CD80 mAb and could also be inhibited by cyclosporine A. Proliferating OT-I cells did not produce IFN-γ, even when re-exposed to mature DC. However, these primed OT-I cells subsequently produced effector cytokines, not just on exposure to their cognate peptide but, more importantly, to weak exogenous TCR agonists that otherwise failed to induce IFN-γ. We further showed that OT-I cells undergoing locally driven proliferation to another pathogen, Streptococcus pneumoniae, rapidly seeded other lymphoid tissues, suggesting that CD8+ T cells primed in this way may play a role in rapidly countering pathogen dissemination.
Fms-Like Tyrosine Kinase 3 Ligand Regulates Migratory Pattern and Antigen Uptake of Lung Dendritic Cell Subsets in a Murine Model of Allergic Airway Inflammation
Authors: Shao Zhifei , Makinde Toluwalope O. , McGee Halvor S. , Wang Xiang , Agrawal Devendra K. 
Published: November 2009

Abstract
Fms-like tyrosine kinase 3 ligand (Flt3L) reverses the features of allergic airway inflammation and increases a Th2-suppressive regulatory lung CD11chighCD11blow dendritic cell (DC) subset in a mouse model. We examined the migratory pattern and Ag uptake efficiency of lung DC subsets in the therapeutic effect of Flt3L. Lung CD11chighCD11blow and CD11clowCD11bhigh DCs from PBS-treated, OVA-sensitized, and Flt3L-treated/OVA-sensitized BALB/c mice were sorted using MACS and FACS for phenotype analysis. Lymphatic chemokine expression in thoracic lymph nodes was determined by immunohistochemistry. Migration of two lung DC subsets to lymphatic chemokines was examined in vitro using a Transwell chemotaxis assay. Labeled Ag was intranasally delivered into mouse lung to track the migration and Ag uptake of lung DCs. The in vitro cytokine secretion of mediastinal lymph node cells was determined using ELISA. CD11clowCD11bhigh DCs have higher expression of CCR5, CCR6, and CCR7, but lower expression of CCR2 than CD11chighCD11blow DCs. CD11clowCD11bhigh DCs in Flt3L-treated/OVA-sensitized mice demonstrated a less mature phenotype, inefficiency in Ag uptake, and impaired migration in vitro to lymphatic chemokine than those in OVA-sensitized mice. Administration of Flt3L decreased the expression of CCR5 and CCR7 in CD11clowCD11bhigh DCs in OVA-sensitized mice. Fewer Ag-carrying cells were detected in the lungs and lymph nodes in Flt3L-treated/OVA-sensitized mice than OVA-sensitized mice with a greater decrease in CD11clowCD11bhigh DCs. Mediastinal lymph node cells from Flt3L-treated mice secreted higher levels of Th1 cytokines and IL-10 than OVA-sensitized mice in vitro. In conclusion, Flt3L-generated lung immunogenic CD11clowCD11bhigh DCs have a less mature phenotype, impaired Ag uptake, and impaired migration to draining lymph nodes.
The Oxazolidinone Derivative Locostatin Induces Cytokine Appeasement
Authors: Ménoret Antoine , McAleer Jeremy P. , Ngoi Soo-Mun , Ray Swagatam , Eddy Nicholas A. , Fenteany Gabriel , Lee Seung-Joo , Rossi Robert J. , Mukherji Bijay , Allen David L. , Chakraborty Nitya G. , Vella Anthony T. 
Published: November 2009

Abstract
Damaging inflammation arising from autoimmune pathology and septic responses results in severe cases of disease. In both instances, anti-inflammatory compounds are used to limit the excessive or deregulated cytokine responses. We used a model of robust T cell stimulation to identify new proteins involved in triggering a cytokine storm. A comparative proteomic mining approach revealed the differential mapping of Raf kinase inhibitory protein after T cell recall in vivo. Treatment with locostatin, an Raf kinase inhibitory protein inhibitor, induced T cell anergy by blocking cytokine production after Ag recall. This was associated with a reduction in Erk phosphorylation. Importantly, in vivo treatment with locostatin profoundly inhibited TNF-α production upon triggering the Ag-specific T cells. This effect was not limited to a murine model because locostatin efficiently inhibited cytokine secretion by human lymphocytes. Therefore, locostatin should be a useful therapeutic to control inflammation, sepsis, and autoimmune diseases.
Neonatal Innate TLR-Mediated Responses Are Distinct from Those of Adults
Authors: Kollmann Tobias R. , Crabtree Juliet , Rein-Weston Annie , Blimkie Darren , Thommai Francis , Wang Xiu Yu , Lavoie Pascal M. , Furlong Jeff , Fortuno Edgardo S. , Hajjar Adeline M. , Hawkins Natalie R. , Self Steven G. , Wilson Christopher B. 
Published: November 2009

Abstract
The human neonate and infant are unduly susceptible to infection with a wide variety of microbes. This susceptibility is thought to reflect differences from adults in innate and adaptive immunity, but the nature of these differences is incompletely characterized. The innate immune response directs the subsequent adaptive immune response after integrating information from TLRs and other environmental sensors. We set out to provide a comprehensive analysis defining differences in response to TLR ligation between human neonates and adults. In response to most TLR ligands, neonatal innate immune cells, including monocytes and conventional and plasmacytoid dendritic cells produced less IL-12p70 and IFN-α (and consequently induced less IFN-γ), moderately less TNF-α, but as much or even more IL-1β, IL-6, IL-23, and IL-10 than adult cells. At the single-cell level, neonatal innate cells generally were less capable of producing multiple cytokines simultaneously, i.e., were less polyfunctional. Overall, our data suggest a robust if not enhanced capacity of the neonate vs the adult white-blood cell TLR-mediated response to support Th17- and Th2-type immunity, which promotes defense against extracellular pathogens, but a reduced capacity to support Th1-type responses, which promote defense against intracellular pathogens.
Cytosolic Aminopeptidases Influence MHC Class I-Mediated Antigen Presentation in an Allele-Dependent Manner
Authors: Kim Eunkyung , Kwak Heechun , Ahn Kwangseog 
Published: November 2009

Abstract
Antigenic peptides presented by MHC class I molecules are generated mainly by the proteasome in the cytosol. Several cytosolic aminopeptidases further trim proteasomal products to form mature epitopes or individual amino acids. However, the distinct function of cytosolic aminopeptidases in MHC class I Ag processing remains to be elucidated. In this study, we show that cytosolic aminopeptidases differentially affect the cell surface expression of MHC class I molecules in an allele-dependent manner in human cells. In HeLa cells, knockdown of puromycin-sensitive aminopeptidase (PSA) by RNA interference inhibited optimal peptide loading of MHC class I molecules, and their cell surface expression was correspondingly reduced. In contrast, depletion of bleomycin hydrolase (BH) enhanced optimal peptide loading and cell surface expression of MHC class I molecules. We did not find evidence on the effect of leucine aminopeptidase knockdown on the MHC class I Ag presentation. Moreover, we demonstrated that PSA and BH influence the peptide loading and surface expression of MHC class I in an allele-specific manner. In the absence of either PSA or BH, the surface expression and peptide-dependent stability of HLA-A68 were reduced, whereas those of HLA-B15 were enhanced. The surface expression and peptide-dependent stability of HLA-A3 were enhanced by BH knockdown, although those of HLA-B8 were increased in PSA-depleted conditions.
TLR Cross-Talk Specifically Regulates Cytokine Production by B Cells from Chronic Inflammatory Disease Patients
Authors: Jagannathan Madhumita , Hasturk Hatice , Liang YanMei , Shin Hyunjin , Hetzel Jeremy T. , Kantarci Alpdogan , Rubin Daniel , McDonnell Marie E. , Van Dyke Thomas E. , Ganley-Leal Lisa M. , Nikolajczyk Barbara S. 
Published: November 2009

Abstract
Chronic systemic inflammation links periodontal disease and diabetes to increased incidence of serious comorbidities. Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. Human B cells have been generally thought to lack these TLRs. However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. New data show that B cells from inflammatory disease patients secrete multiple cytokines in response to different classes of TLR ligands. Furthermore, the B cell response to combinations of TLR ligands is cytokine- and ligand-specific. Some cytokines (IL-1β and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-α) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. Parallel examination of B cells from periodontal disease and diabetes patients suggested that outcomes of TLR cross-talk are influenced by disease pathology. We conclude that disease-associated alteration of B cell TLR responses specifically regulates cytokine production and may influence chronic inflammation.