Downregulation of Orai1 expression in the airway alleviates murine allergic rhinitis

Orai1 is the key subunit of the Ca2+-release-activated Ca2+ channel. Our previous report has demonstrated that Orai1 expression in the airway was upregulated in the ovalbumin (OVA)-induced allergic rhinitis (AR) mouse models. To observe whether inhibition of Orai1 expression in the airway could suppress symptoms in a murine model of AR and to assess the impacts of this inhibition on the responses of local and systemic immunocytes, we administered recombinant lentivirus vectors that encoded shRNA against ORAI1 (lenti-ORAI1) into the nostrils of OVA-sensitized mice before the challenges, and analyzed its effect on allergic responses, as compared with the unsensitized mice and untreated AR mice. Administration of lenti-ORAI1 into the nasal cavity successfully infected cells in the epithelial layer of the nasal mucosa, and significantly decreased the frequencies of sneezing and nasal rubbing of the mice. Protein levels of leukotriene C4, OVA-specific IgE, and IL-4 in the nasal lavage fluid and serum and eosinophil cation protein in the serum were also significantly reduced by lenti-ORAI1, as were the mRNA levels of these factors in the nasal mucosa and spleen. These data suggested that administration of lenti-ORAI1 into the nasal cavity effectively decreased Orai1 expression in the nasal mucosa, alleviated AR symptoms, and partially inhibited the hyperresponsiveness of the local and systemic immune cells including T cells, B cells, mast cells and eosinophils that are involved in the pathogenesis of AR.

Molecular variations in Th1-specific cell surface gene Tim-3

The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, Tim-3 (T cell immunoglobulin mucin 3) is selectively expressed on the surface of differentiated Th1 cells. Tim-3 might have an important role in the induction of autoimmune diseases by regulating macrophage activation and interacts with Tim-3 ligand to regulate Th1 responses. To determine the variation sites in the coding and promoter region of human Tim-3 gene, we performed variation scanning by direct sequencing using the genomic DNA isolated from the patients with asthma or allergic rhinitis and healthy controls without asthma and allergic rhinitis. We identified four single nucleotide polymorphisms (SNPs) including one novel SNPs (-1541C>T) and two variation sites (-1292_-1289delTAAA and -1282_-1278dupTAAAA) in the coding and promoter region of human Tim-3 gene in both the patients and healthy groups.

Determinacion serica de los niveles de ICAM-1s en pacientes con rinitis alergica / Serum levels of ICAM-1s in patient with allergic rhinitis

Se presume que la molécula de adhesión intercelular -1 (ICAM-1, CD54) está involucrada en la patogénesis del asma y se ha detectado una forma soluble de ICAM-1 (ICAM-1 s) en concentraciones elevadas en el suero de pacientes con ciertas condiciones inflamatorias. En este estudio, examinamos los niveles de ICAM-1 soluble en pacientes con rinitis alérgica de diversos grados: leve (8 pacientes), moderada (12 pacientes), severa (15 pacientes), del instituto de alergias, asma e inmunología. Los resultados fueron luego comparados con 10 sujetos saludables, como control negativo, sin diagnóstico de rinitis alérgica ni asma, y con 10 sujetos con asma de la unidad de neumología del Hospital La Samaritana, como control positivo. Todos los pacientes con edades entre 15 y 55 años. Utilizamos la técnica ELISA para medir ICAM-ls. Con anterioridad, todos los pacientes fueron sometidos a una prueba alérgica mediante el método Prick. Nuestro objetivo fue analizar si ICAM-1 s es un marcador de la severidad de la rinitis alérgica, y encontramos que los niveles de ICAM-1 soluble muestran un incremento a medida que la rinitis alérgica progresa. La comparación entre el grupo general de rinitis alérgica y el grupo de control negativo muestra resultados estadísticamente significativos (P < 0.05) y cada uno de los grupos de rinitis alérgica (leve, moderada y severa) en relación con el control negativo mostró que la expresión de ICAM-1 no incrementa y se mantiene baja, (Rinitis Leve p = 0.495, Moderada p = 0.0017, Severa p = 0.0014). Los anteriores resultados confirman nuestra hipótesis