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Epidemiology of Asthma
Published in Jonathan A. Bernstein, Mark L. Levy, Clinical Asthma, 2014
The role of genetic variants as risk factors in the population in determining the geographical distribution of asthma prevalence should be noted. Fundamentally, much of asthma is likely to result from the effects of environmental factors on genetically susceptible persons. Allergic IgE-mediated asthma is strongly familial with the heritability of asthma being 75%.36 Studies in identical twins have also demonstrated that 50% of the susceptibility to asthma is due to genetic determinants.37 GWAS have found genes that may play a role in the development of asthma, for instance, the null allele for the gene encoding filaggrin (2282del4 and R501X).38 Filaggrin is expressed in the outer epidermis and the oral and nasal mucosa, and helps in the formation of the epithelial barrier, which may impede allergen entry and thereby prevent allergic sensitization. Other GWAS studies have found genes related to asthma, including ORMDL3, which belongs to a family of genes that encode transmembrane proteins anchored in the endoplasmic reticulum.39CCR5Delta32, which is thought to control pathogen entry into cells, has been found to be associated with asthma in childhood, but not adults.40 The ADAM33 gene has a role in the production of ADAM proteins. The ADAM proteins are membrane-anchored metalloproteases with diverse functions, including the shedding of cell-surface proteins such as cytokines and cytokine receptors, which play a role in asthma.41 It is also possible that variations in asthma may be due to differences in the proportion of individuals in different ethnic groups who carry known or hitherto unknown genetic polymorphisms42 and that ethnic variability exists in important gene defects such as filaggrin.38
Local delivery of interleukin 7 with an oncolytic adenovirus activates tumor-infiltrating lymphocytes and causes tumor regression
Published in OncoImmunology, 2022
Tatiana V. Kudling, James H.A. Clubb, Dafne C.A. Quixabeira, Joao M. Santos, Riikka Havunen, Alexander Kononov, Camilla Heiniö, Victor Cervera-Carrascon, Santeri Pakola, Saru Basnet, Susanna Grönberg-Vähä-Koskela, Victor Arias, Ivan Gladwyn-Ng, Katri Aro, Leif Bäck, Jari Räsänen, Ilkka Ilonen, Kristian Borenius, Mikko Räsänen, Otto Hemminki, Antti Rannikko, Anna Kanerva, Johanna Tapper, Akseli Hemminki
The analysis of the tumor microenvironment showed a clear shift toward proinflammatory signaling in ex vivo patient samples infected with Ad5/3-E2F-d24-hIL7, particularly, increased IFNg production, which, in turn, stimulates expression of Ccl5, Cxcl9 and Cxcl10 – key chemokines involved in the recruitment of T cells and NK cells. Indeed, we observed higher number of CD4+ and CD8+ migrated cells when used supernatants obtained after infection with IL7 armed virus. Transcriptomic analysis showed upregulation of several migration-related genes in CD4+ cells – CCR5, DPP4, ITGA4, MYO1G. Interestingly, we observed significant upregulation of ADAM19 gene in both CD4+ and CD8 + T cell, however, the role of this particular protein in immune cells is still unclear. ADAM proteins are membrane disintegrins and metalloproteinases, which convert nearby membrane-anchored cytokine precursors, cytokine receptors, Notch receptors, phagocytic receptors or cell adhesion molecules into soluble bioactive mediators.31 In T cells, ADAMs can be involved in cell development and activation via cleavage of negative regulatory proteins, such as LAG3,32 and regulate cell migration not only due to the proteolytic activity of ADAMs on the T cells themselves, but also due to the protease activity on the tissue cells serving as substrate of cell migration.33 Nevertheless, additional experiments are needed to understand the role of ADAM19 in T cells activation and migration upon Ad5/3-E2F-d24-hIL7 infection.
The role of ADAM-like decysin 1 in non-eosinophilic chronic rhinosinusitis with nasal polyps
Published in Acta Oto-Laryngologica, 2018
Naoki Sugimoto, Tsuguhisa Nakayama, Yoshiyuki Kasai, Daiya Asaka, Ryoto Mitsuyoshi, Tadao Tsurumoto, Shinya Takaishi, Sachiko Omae, Hiromi Kojima, Yasuhiro Tanaka, Shin-Ichi Haruna
A disintegrin and metalloprotease (ADAM)-like decysin 1 (ADAMDEC1) is a unique member of the ADAM protein family of transmembrane and secreted proteins. These proteins function in cell adhesion and proteolytic processing of the ectodomains of diverse cell surface receptors and signalling molecules [13]. ADAMDEC1 is a member of the ADAM subfamily D and is referred to as ‘ADAM-like’ because it is structurally distinct from other ADAM family members [14]. Although the functions of ADAMDEC1 are not well understood, it has been reported to play roles in tissue repair and immunity, particularly at the early stages of the inflammatory response [15,16]. In addition, ADAMDEC1 has been associated with Crohn’s disease [16], atherosclerotic plaques [17], pulmonary sarcoidosis [18], and craniopharyngioma [19]. This study aims to investigate our hypothesis that ADAMDEC1 expression in polyp tissue may play a role in the pathogenesis of CRS.
ADAM17 regulates the proliferation and extracellular matrix of keloid fibroblasts by mediating the EGFR/ERK signaling pathway
Published in Journal of Plastic Surgery and Hand Surgery, 2023
A disintegrin and metalloprotease protein 17 (ADAM17), belonging to the ADAM protein family, is a transmembrane zinc-dependent metalloprotease implicated in diverse biological processes, including cell migration and adhesion [8]. ADAM17 was shown to be crucial for protecting the skin barrier via proteolytic activation of epidermal growth factor receptor (EGFR) ligand, which can bind to the extracellular part of EGFR to activate EGFR tyrosine kinase and the corresponding downstream signaling pathways (such as extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38), thus playing a role in regulating the pathological process of inflammation and tumors [9,10]. As reported, EGFR is very important for wound healing of the skin, and in particular, it is also the basement substance of ADAM17, which could work jointly to maintain complete skin development [11]. In addition, activation of the EGFR/ERK pathway was observed to take part in transforming growth factor-β (TGF-β)-dependent renal fibrosis [12]. Transforming growth factor-β1 (TGF-β1) has been credited as the most powerful profibrotic cytokine since it can aggravate keloid formation by regulating fibroblast formation and inhibiting the degradation of collagen and other ECM proteins [13]. Evidence has pointed out the role of ADAM17/EGFR-dependent ERK activation in mediating thrombin-stimulated connective tissue growth factor (CTGF) expression in human lung fibroblasts, and consequently, silencing ADAM17 could alleviate the degree of lung fibrosis [14]. Hence, we speculated that ADAM17 may play a regulatory role in keloid fibroblasts (KFs) by mediating the EGFR/ERK pathway.