920 resultados para ALLERGY
Resumo:
Langerhans cells (LCs) are prominent dendritic cells (DCs) in epithelia, but their role in immunity and tolerance is poorly defined. 'Knockin' mice expressing enhanced green fluorescent protein (EGFP) under the control of the langerin (CD207) gene were recently developed in order to discriminate epidermal LCs from other DC subsets and at the same time to track their dynamics under steady-state or inflammatory conditions in vivo. Additional knockin mice expressing a diphtheria toxin receptor fused to EGFP were used to conditionally ablate LCs and assess their role in triggering hapten-specific T cell effectors through skin immunization. We review the insights that have been provided by these various knockin mice and discuss gaps in our knowledge of LCs that need to be filled.
Resumo:
Osteopontin (OPN) is a predominantly secreted extracellular matrix glycophosphoprotein which binds to alpha v-containing integrins and has an important role in malignant cell attachment and invasion. High OPN expression in the primary tumor is associated with early metastasis and poor outcome in human breast and other cancers. Forced OPN overexpression in benign cells may induce neoplastic-like cell behaviour including increased attachment and invasion in vitro as well as the ability to metastasize in vivo. Conversely, OPN inhibition by antisense cDNA impedes cell growth and tumor forming capacity. OPN is not mutationally activated in cancer but its expression is regulated by Wnt/Tcf signaling, steroid receptors, growth factors, ras, Ets and AP-1 transcription factors. Presumably these factors are implicated in induction of OPN overexpression in cancer. Greater understanding of the role of OPN in neoplastic change and its transcriptional regulation may enable development of novel cancer treatment strategies
Resumo:
Pregnancy is proposed to be a Th2 phenomenon, where Th2 cytokines inhibit Th1 responses to improve fetal survival. The importance of interleukin-10 (IL-10), an immunomodulatory cytokine produced by Th2 cells, in the maintenance of normal pregnancy is becoming increasingly apparent. In a longitudinal case-control study, the physiological effect of pregnancy on plasma IL-10 was investigated. The plasma concentration of IL-10 was determined using an ELISA technique in 99 pregnant women sampled at 12, 20 and 35 weeks of gestation, 38 non-pregnant control subjects sampled in parallel and in a subgroup of women sampled at 3 days post-partum (n, pregnant 21, non-pregnant 21). Plasma IL-10 was significantly higher in pregnant women at 12, 20 and 35 weeks of gestation (p
Resumo:
Background The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC) uses a Nasal Allergen Challenge (NAC) model to study the pathophysiology of AR and provides proof of concept for novel therapeutics. The NAC model needs to ensure optimal participant qualification, allergen challenge, clinical symptoms capture and biological samples collection. Repeatability of the protocol is key to ensuring unbiased efficacy analysis of novel therapeutics. The effect of allergen challenge on IL-33 gene expression and its relation to IL1RL1 receptor and cytokine secretion was investigated. Methods Several iterations of the NAC protocol was tested, comparing variations of qualifying criteria based on the Total Nasal Symptom Score (TNSS) and Peak Nasal Inspiratory Flow (PNIF). The lowest allergen concentration was delivered and TNSS and PNIF recorded 15 minutes later. Participants qualified if the particular criteria for the protocol were met, otherwise the next higher allergen concentration (4-fold increase), was administered until the targets were reached. Participants returned for a NAC visit and received varying allergen challenge concentrations depending on the protocol, TNSS/PNIF were recorded at 15 minutes, 30 minutes, 1 hour, and hourly up to 12 hours, a 24 hour time point was added in later iterations. Repeatability was evaluated using a 3-4week interval between screening, NAC1, and NAC2 visits. Various biomarker samples were collected. Results A combined TNSS and PNIF criterion was more successful in qualifying participants. The cumulative allergen challenge (CAC) protocol proved more reliable in producing a robust clinical and biomarker response. Repeatability of the CAC protocol was achieved with a 3-week interval between visits, on a clinical and biological basis. IL-33 cytokine is an important biomarker in initiating the inflammatory response in AR in humans. IL-33 and IL1RL1 expression might employ a negative feedback mechanism in human nasal epithelial cells. Comparing the clinical and biological response to ragweed vs cat allergen challenge, proved the CAC protocol’s suitability for use employing different allergens. Conclusion The AR-CIC’s CAC protocol is an effective method of studying AR, capable of generating measurable and repeatable clinical and biomarker responses, enabling better understanding of AR pathophysiology and ensuring that any change would be purely due to medication under investigation in a clinical trial setting.