1,721,075 research outputs found
Fibrosis in ocular allergic inflammation: recent concepts in the pathogenesis of ocular allergy
No full textPURPOSE OF REVIEW:
Mast cells and eosinophils are the main effector cells in allergic inflammation, but there is now compelling evidence that fibroblasts are also important players in the inflammatory response. In fact, they respond to different stimuli and release several mediators that modulate mast-cell and eosinophil functionality. In several allergic conditions such as vernal keratoconjunctivitis, asthma and atopic dermatitis the chronic presence of the inflammatory process has been associated with fibrosis and tissue remodeling, which in turn could cause irreversible alterations in the organ anatomy and functions. This review will discuss current advances in mast cell, eosinophil and fibroblast interactions in terms of their importance in the perpetuation of allergic inflammation and in contributing to the fibrosis and/or remodeling process in ocular allergy. As a main example of allergic ocular diseases associated with fibrosis, vernal keratoconjunctivitis is discussed in the light of recent findings.
RECENT FINDINGS:
Several studies have recently shown that fibroblasts can modulate the functions of mast cells and eosinophils through the membrane form of stem cell factor and granulocyte-macrophage colony-stimulating factor, respectively. On the other hand, fibroblasts can be affected by inflammatory mediators derived from mast cells and eosinophils, such as transforming growth factor beta and nerve growth factor and by the T helper type 2 cytokines, IL-4 and IL-13, and vernal keratoconjunctivitis-derived fibroblasts display altered functions.
SUMMARY:
Considerable useful information has been gained about the role of mast cells, eosinophils and fibroblasts in the perpetuation of allergic inflammation and tissue fibrosis and/or remodeling in general, and specifically in ocular allergy
New insights on the involvement of Nerve Growth Factor in allergic inflammation and fibrosis
No full textNerve Growth Factor (NGF), that was originally discovered for its properties of stimulating growth and differentiation of neurons, is now also considered responsible for several activities in the immune system and beyond. Mast cells and eosinophils, key cells of allergic inflammation, are a source of NGF and are influenced by it. These observations have prompted studies on NGF in allergy and tissue repair. Recent evidences link NGF and these two processes. While NGF is clearly a new tool in the management of untreatable ulcers, its role in allergic inflammation, although appearing to be pro-inflammatory, is still not clearly defined
Mast cells in allergy and beyond
No full textMast cells (MC) are highly granulated tissue dwelling cells, widely distributed throughout the body in connective tissues and on mucosal surfaces. They are derived from bone marrow progenitors that migrate into the blood and subsequently into the tissues, where they undergo final maturation. Mast cell proliferation, differentiation, survival and activation are regulated by stem cell factor, the ligand for the c-kit tyrosine kinase receptor, expressed on the mast cell surface. They release a large number of pro-inflammatory and immunoregulatory mediators after activation induced by either immunoglobulin E-dependent or immunoglobulin E-independent mechanisms. Mast cells have been most widely studied in the context of allergic reactions and parasite infections, but there is now compelling evidences that they are important players in innate and acquired immunity, wound healing, fibrosis, tumors and autoimmune diseases. This review will discuss current advances in these fields
Reduced eosinophil pro-fibrogenic effect in severe childhood asthma compared to mild disease: an effect of corticosteroids?
No full textEosinophils play an important role in inflammation and probably in airway remodeling in asthma. We previously demonstrated that eosinophils from atopic subjects display pro-fibrogenic properties towards lung fibroblasts partially by preformed transforming growth factor-beta (TGF-beta). We hypothesized that the pro-fibrogenic potential of eosinophils is increased in children with life-threatening asthma (LTA). Six children with atopic LTA clinically well-controlled by inhaled corticosteroids (ICS) and 5 children with atopic mild asthma (MA) treated only with inhaled beta(2)-agonists were investigated. The effects of their peripheral blood eosinophils on fibroblast proliferation and lattice contraction were investigated. In addition, TGF-beta(1) and IL-6 eosinophil content were also evaluated. Unexpectedly, eosinophils from LTA increased fibroblast proliferation (5.4-fold) and gel contraction (1.1-fold) significantly less than those from MA. TGF-beta(1) but not IL-6 eosinophil content in LTA was significantly lower than that in MA (2.7-fold). In vitro, addition of dexamethasone on eosinophils stimulated by mast cells resulted in a marked decrease in their TGF-beta(1) content by 1.6-fold. In conclusion, eosinophils from children with ICS-treated LTA displayed significantly less pro-fibrogenic properties than those from MA treated only with beta(2)-agonists. Our data suggest that the pro-fibrogenic effect of eosinophils might be influenced by treatment with ICS in childhood asthma
Therapeutic approaches in allergic diseases
No full textAllergic diseases are a group of immune-mediated disorders mainly caused by an IgE-dependent immunological reaction to an innocuous environmental antigen (allergen). According to the site of contact with the allergen, different clinical manifestations may develop in the airways, skin or gastrointestinal tract. The frequency of allergic diseases is increased over the last century. Because of their frequency and their impact on the quality of life, new therapeutic approaches for these disorders have been the object of intensive research. Thus, the past 10 years witnessed the development and evaluation of a number of drugs that target IgE, Th-2 cytokines, mast cells and eosinophils.
This chapter will briefly review the strategies to treat allergic diseases, targeting the different steps of IgE hypersensitivity reactions: down-modulation of T and B responses to allergen, blocking of IgE effector function, modulation of cytokines/cytokine receptors, inhibition of mast cells and eosinophils activities
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