1,721,021 research outputs found
Nerve growth factor involvement in the visual system: implications in allergic and neurodegenerative diseases
No full textThe purpose of this review is to outline the main role of nerve growth factor (NGF) in the visual system and particularly in the ocular surface in physiological and pathological conditions. The present review of experimental and clinical studies will highlight old and recent strategies for treating ocular surface and tear disorders with NGF
BI-SPECIFIC COMPLEXES FOR TARGETING CELLS INVOLVED IN ALLERGIC-TYPE REACTIONS, COMPOSITIONS AND USES THEREOF
No full textNerve growth factor and tissue repair remodeling: trkA(NGFR) and p75(NTR), two receptors one fate
No full textThis review deals with the role of nerve growth factor (NGF) in healing process as a result of injury. The role of both trkA(NGFR) and p75(NTR) specific NGF receptors and their contribution in the complex network of tissue repair process, is discussed and highlighted in view of recent findings. In fact, NGF represents a significant advance in the treatment of etiologically different ulcers (corneal ulcers, pressure ulcers, post-viral infections, chemical burns) and might shorten the recovery process. For these diseases, no specific treatment is actually available. It is reasonable that apart from NGF and/or neurotrophins a different time-course of trkA(NGRF)/p75(NTR) expression, might regulate the final process. In summary, these novel findings on the potential pro-healing capacity of NGF might open new possibilities for this growth factor in modulating the healing processes in several pathological conditions
Bidirectional Mast Cell–Eosinophil Interactions in Inflammatory Disorders and Cancer
Full text linkHuman mast cells (MCs) and eosinophils were first described and named by Paul Ehrlich. These cells have distinct myeloid progenitors and differ morphologically, ultrastructurally, immunologically, biochemically, and pharmacologically. However, MCs and eosinophils play a pivotal role in several allergic disorders. In addition, these cells are involved in autoimmune disorders, cardiovascular diseases, and cancer. MCs are distributed throughout all normal human tissues, whereas eosinophils are present only in gastrointestinal tract, secondary lymphoid tissues, and adipose tissue, thymus, mammary gland, and uterus. However, in allergic disorders, MCs and eosinophils can form the “allergic effector unit.” Moreover, in several tumors, MCs and eosinophils can be found in close proximity. Therefore, it is likely that MCs have the capacity to modulate eosinophil functions and vice versa. For example, interleukin 5, stem cell factor, histamine, platelet-activating factor (PAF), prostaglandin D2 (PGD2), cysteinyl leukotrienes, and vascular endothelial growth factors (VEGFs), produced by activated MCs, can modulate eosinophil functions through the engagement of specific receptors. In contrast, eosinophil cationic proteins such as eosinophil cationic protein and major basic protein (MBP), nerve growth factor, and VEGFs released by activated eosinophils can modulate MC functions. These bidirectional interactions between MCs and eosinophils might be relevant not only in allergic diseases but also in several inflammatory and neoplastic disorders
Food allergy as a risk factor for life-threatening asthma in childhood: a case-controlled study
No full textBackground: No objective clinical risk factors exist for pediatric life-threatening asthma. Objectives: In this study, we address whether persistent food allergy and degree of atopy are risk factors for life-threatening asthma. Methods: By use of a case-controlled design, children (1-16 years) ventilated for an exacerbation of asthma were enrolled. Each case was matched by sex, age, and ethnicity, with 2 controls who had attended with a non–life-threatening exacerbation. All subjects were assessed by means of a questionnaire, spirometry, and skin prick or RAST testing. The data were analyzed by conditional logistic regression. Results: Nineteen cases and 38 controls were enrolled. Compared with controls, cases were found to have the following risk factors: food allergy (odds ratio, 8.58; 95% CI, 1.85-39.71), multiple allergic diagnoses (4.42; 1.17-16.71), early onset of asthma (6.48; 1.36-30.85), and frequent admissions (14.2; 1.77-113.59). After regression analysis, only frequent admission with asthma (9.85; 1.04-93.27) and food allergy (5.89; 1.06-32.61) were independently associated with life-threatening asthma. Half the cases had food allergy compared with only 10% of controls. Conclusion: This study demonstrates that poorly controlled asthma and food allergy are significant risk factors for life-threatening asthma. More intensive management of this high-risk group of children might help to reduce future morbidity and mortality
Human mast cells undergo TRAIL-induced apoptosis
No full textMast cells (MC), supposedly long-lived cells, play a key role in allergy and are important contributors to other inflammatory conditions in which they undergo hyperplasia. In humans, stem cell factor (SCF) is the main regulator of MC growth, differentiation, and survival. Although human MC numbers may also be regulated by apoptotic cell death, there have been no reports concerning the role of the extrinsic apoptotic pathway mediated by death receptors in these cells. We examined expression and function of death receptors for Fas ligand and TRAIL in human MC. Although the MC leukemia cell line HMC-1 and human lung-derived MC expressed both Fas and TRAIL-R, MC lines derived from cord blood (CBMC) expressed only TRAIL-R. Activation of TRAIL-R resulted in caspase 3-dependent apoptosis of CBMC and HMC-1. IgE-dependent activation of CBMC increased their susceptibility to TRAIL-mediated apoptosis. Results suggest that TRAIL-mediated apoptosis may be a mechanism of regulating MC survival in vivo and, potentially, for down-regulating MC hyperplasia in pathologic conditions
Nerve growth factor effect on human primary fibroblastic-keratocytes: possible mechanism during corneal healing
No full textIn response to corneal injury, cytokines and growth factors play a crucial role by influencing epithelial-stromal interaction during the healing and reparative processes which may resolve in tissue remodeling and fibrosis. While transforming growth factor-beta1 (TGF-beta1) is considered the main profibrogenic modulator of these process, recently the nerve growth factor (NGF) appears as a pleiotropic modulator of wound-healing and inflammatory responses. Interestingly in the cornea, where NGF, trkA(NGFR) and p75(NTR) are expressed by epithelial cells and keratocytes, the NGF eye-drop induces the healing of neurotrophic or autoimmune corneal ulcers. During corneal healing, quiescent keratocytes are replaced by active fibroblast-like keratocytes/myofibroblasts. While the NGF effect on epithelial cells has been investigated, no data are reported for NGF effects on fibroblastic-keratocytes, during corneal healing. NGF, trkA(NGFR) and p75(NTR) were found expressed by fibroblastic-keratocytes. NGF was able to induce fibroblastic-keratocyte differentiation into myofibroblasts, migration, Metalloproteinase-9 expression/activity and contraction of a 3D collagen gel, without affecting their proliferation and collagen production. These data also show a two-directional control of fibroblastic-keratocytes by NGF and TGF-beta1. To sum up, the findings of this study indicate that NGF can modulate some functional activities of fibroblastic-keratocytes, thus substantiating the healing effects of NGF on corneal wound-healing
Safety of humanized monoclonal antibodies against IL-5 in asthma: focus on reslizumab
No full textReslizumab, a humanized mAb against IL-5, reduces the number of eosinophils in the blood and lungs. Based on efficacy and safety data from pivotal RCTs, reslizumab had been approved for use as an add-on maintenance treatment of severe asthma with an eosinophilic phenotype in adults who have a history of exacerbations despite receiving their current asthma medicines. Areas covered: Current literature on reslizumab has been reviewed with a specific focus on its safety profile in the treatment of severe asthma. Expert opinion: Large pivotal and supportive trials reinforce the view that reslizumab is well tolerated, with an acceptable safety profile in patients exposed for longer than 2 years. However, no or few data concerning safety in special populations such as smokers, those with immune- and cellular senescence, patients with comorbidities and those receiving multi-drug treatments are available as yet. Furthermore, we need to fully elucidate some fundamental issues such as the risk of anaphylaxis and the long-term risk-benefit ratio of the impact of depletion of eosinophils and the potential risk of malignancies induced by a treatment with this anti-IL-5 agent
Human mast cells express intracellular TRAIL
No full textRecently we demonstrated that human mast cells (MC) express functional TRAIL death receptors. Here we assessed the expression of TRAIL on both mRNA and protein level in cord blood derived MC (CBMC) and HMC-1. The TRAIL release either spontaneous or induced by LPS, IFN-gamma and IgE-dependent activation, was evaluated as well. The protein location was restricted to the intracellular compartment in CBMC, but not in HMC-1. The intracellular TRAIL was not localized inside the granules. The treatment with IFN-gamma and LPS up-regulated intracellular TRAIL expression in CBMC, but did not induce its release. These in vitro data show that human MC can produce and express intracellular TRAIL whose location could not be altered by different stimuli
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