IL-5 and IL-5 receptor in asthma

Abstract

and a soluble isoform (αIL-5Rs). Cytokines such as IL-5 produce specific and non-specific cellular responses through specific cell membrane receptor mediated activation of intracellular signal transduction pathways which, to a large part, regulate gene expression. The major intracellular signal transduction mechanism is activation of non-receptor associated tyrosine kinases including JAK and MAP kinases which can then transduce signals via a novel family of transcriptional factors named signal transducers and activators of transcription (STATS). JAK2, STAT1 and STAT 5 appear to be particularly important in IL-5 mediated eosinophil responses. Asthma is characterized by episodic airways obstruction, increased bronchial responsiveness, and airway inflammation. Several studies have shown an association between the number of activated T cells and eosinophils in the airways and abnormalities in FEV1, airway reactivity and clinical severity in asthma. It has now been well documented that IL-5 is highly expressed in the bronchial mucosa of atopic and intrinsic asthmatics and that the increased IL-5 mRNA present in airway tissues is predominantly T cell derived. Immunocytochemical staining of bronchial biopsy sections has confirmed that IL-5 mRNA transcripts are translated into protein in asthmatic subjects. Furthermore, the number of activated CD 4 + T cells and IL-5 mRNA positive cells are increased in asthmatic airways following antigen challenge and studies that have examined IL-5 expression in asthmatic subjects before and after steroids have shown significantly decreased expression following oral corticosteroid treatment in steroid-sensitive asthma but not in steroid resistant and chronic severe steroid dependent asthma. The link between T cell derived IL-5 and eosinophil activation in asthmatic airways is further strengthened by the demonstration that there is an increased number of αIL-5R mRNA positive cells in the bronchial biopsies of atopic and non-atopic asthmatic subjects and that the eosinophil is the predominant site of this increased

Differential Engagement of Modules 1 and 4 of Vascular Cell Adhesion Molecule-1 (CD106) by Integrins α4β1 (CD49d/29) and αMβ2 (CD11b/18) of Eosinophils

“…Such EOS recruited to the asthmatic airway exhibit increased ␣M␤2 expression compared with EOS in blood (78 -80). Activation of ␣M␤2 (45,77) and formation of podosomes of EOS (25), structures believed important in cell migration (70), are induced by exposure to IL-5, which is up-regulated in the blood and airway of human asthmatics (42,(81)(82)(83). In addition, the chemokines RANTES (regulated on activation, normal T-cell expressed and secreted), monocyte chemotactic protein-3, and complement activation factor-5 expose an activation-sensitive epitope of ␣M␤2 (84) and promote migration of blood EOS (84 -87).…”

Bi-Directional Activation Between Human Airway Smooth Muscle Cells and T Lymphocytes: Role in Induction of Altered Airway Responsiveness

“…Bronchial asthma is characterized by exaggerated agonist-induced bronchoconstriction, attenuated ␤-adrenoceptor-mediated airway relaxation and airway inflammation, the latter principally involving infiltration of the airways with T lymphocytes, mast cells, and eosinophils (1)(2)(3)(4)(5)(6)(7)(8)(25)(26)(27)(28). Although the mechanistic interplay between airway inflammation and the associated changes in ASM responsiveness remains to be fully characterized, the wealth of evidence accumulated to date suggests that the altered airway responsiveness in asthma is primarily attributed to the actions of various cytokines, which are primarily produced by infiltrating CD4 ϩ T lymphocytes expressing the Th2 profile of cytokine release (1-8, 27, 28).…”

Efeito da mitomicina C na secreção de fator estimulador de granulócitos macrófagos e interleucina-5 em cultura de estroma de pólipos nasais eosinofílicos

“…In many different studies, eosinophils are considered the main cells involved in the genesis of these diseases. 5,6 Thus, in these studies, we considered to be value any type of eosinophilic NSP, and there was no distinction among the studied cases. Kramer et al (2000) 17 suggested that the mechanisms involved in the genesis of eosinophilic polyposis, of allergic origin or not, are similar.…”

“…Such cytokines, associated with eosinophils, acquire a key role in the pathophysiology of eosinophilic NSP. [2][3][4][5][6] The use of MMC is extremely important because it is an antineoblastic and antibiotic drug that acts as an alkylating agent, inhibiting DNA, protein synthesis and fibroblasts in cell cultures. MMC has been experimentally used in the prevention of stenosis in maxillary antrostomies, glaucoma surgery and pterygiums, in myringotomy and in laryngeal stenosis.…”