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1.
Allergy, Asthma & Immunology Research ; : 677-690, 2019.
Article Dans Anglais | WPRIM | ID: wpr-762154

Résumé

PURPOSE: Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. METHODS: ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. RESULTS: We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4+ effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. CONCLUSIONS: These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.


Sujets)
Animaux , Humains , Souris , Molécule d'adhérence cellulaire des leucocytes activés , Cellules dendritiques , Eczéma atopique , Expression des gènes , Immunoglobulines , Synapses immunologiques , Noeuds lymphatiques , Ovalbumine , Peau , Lymphocytes T , Eau
2.
Yonsei Medical Journal ; : 1222-1231, 2018.
Article Dans Anglais | WPRIM | ID: wpr-719241

Résumé

PURPOSE: Cockroach exposure is a pivotal cause of asthma. Tight junctions are intercellular structures required for maintenance of the barrier function of the airway epithelium, which is impaired in this disease. Matrix metalloproteinases (MMPs) digest extracellular matrix components and are involved in asthma pathogenesis: MMP1 is a collagenase with a direct influence on airway obstruction in asthmatics. This study aimed to investigate the mechanism by which German cockroach extract (GCE) induces MMP1 expression and whether MMP1 release alters cellular tight junctions in human airway epithelial cells (NCI-H292). MATERIALS AND METHODS: mRNA and protein levels were determined using real-time PCR and ELISA. Tight junction proteins were detected using immunofluorescence staining. Epithelial barrier function was measured by transepithelial electrical resistance (TEER). The binding of a transcription factor to DNA molecules was determined by electrophoretic mobility shift assay, while the levels of tight junction proteins and phosphorylation were determined using Western blotting. RESULTS: GCE was shown to increase MMP1 expression, TEER, and tight junction degradation. Both an inhibitor and small interfering RNA (siRNA) of MMP1 significantly decreased GCE-induced tight junction disruption. Furthermore, transient transfection with ETS1 and SP1 siRNA, and anti-TLR2 antibody pretreatment prevented MMP1 expression and tight junction degradation. An extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor also blocked MMP1 release, ETS1/SP1 DNA binding, and tight junction alteration. CONCLUSION: GCE treatment increases MMP1 expression, leading to tight junction disruption, which is transcriptionally regulated and influenced by the ERK/MAPK pathway in airway epithelial cells. These findings may contribute to developing novel therapeutic strategies for airway diseases.


Sujets)
Humains , Obstruction des voies aériennes , Asthme , Blattellidae , Technique de Western , Blattes , Collagenases , ADN , Impédance électrique , Test de retard de migration électrophorétique , Test ELISA , Cellules épithéliales , Épithélium , Matrice extracellulaire , Technique d'immunofluorescence , Matrix metalloproteinase 1 , Matrix metalloproteinases , Phosphorylation , Phosphotransferases , Protein kinases , Réaction de polymérisation en chaine en temps réel , ARN messager , Petit ARN interférent , Protéines de la jonction serrée , Jonctions serrées , Facteurs de transcription , Transfection
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