RESUMEN
Asthma is a common respiratory immune disease in children and adults, and interleukin-4 (IL-4) is one of the key factors for the onset of asthma. Therefore, targeting human IL-4 and IL-4 receptor alpha (IL-4RA) has become one of the strategies for targeted therapy of cytokines. Herein, we established an animal model of asthmatic airway inflammation using double humanized IL-4/IL-4RA (hIL-4/hIL-4RA) mice, where human IL-4 and IL-4RA replaced their murine counterparts, respectively. We successfully identified the phenotype by Southern blotting, ELISA, and flow cytometry. The hIL-4/hIL-4RA mice induced by ovalbumin (OVA) exhibited several important features of asthma, such as inflammatory cell infiltration, IgE release, goblet cell hyperplasia, and Th2 cytokine secretion. Furthermore, treatment of these humanized mice with anti-human IL-4RA antibodies significantly inhibited level of these pathological indicators. Thus, hIL-4/hIL-4RA mice provide a validated preclinical mouse model to interrogate new therapeutic agents targeting this specific cytokine pathway in asthma.
Asunto(s)
Asma/inmunología , Modelos Animales de Enfermedad , Subunidad alfa del Receptor de Interleucina-4/genética , Subunidad alfa del Receptor de Interleucina-4/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Alérgenos/inmunología , Animales , Anticuerpos Monoclonales/uso terapéutico , Asma/sangre , Asma/tratamiento farmacológico , Líquido del Lavado Bronquioalveolar/inmunología , Células Cultivadas , Femenino , Edición Génica , Células Caliciformes/efectos de los fármacos , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Leucocitos/inmunología , Pulmón/inmunología , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Moco/inmunología , Ovalbúmina/inmunología , Bazo/citologíaRESUMEN
To study the CTL antigen epitopes and drug resistance mutations of HIV-1 gag and pol genes through analyzing gag and pol gene sequences. The HIV-1 gag and pol gene fragments were amplified using nested polymerase chain reaction. A total of 23 PCR sequences, 449 cloned gag sequences and 402 cloned pol sequences were obtained. Sequence analyses showed the 23 samples were subtype B or B'. A total of 4 in 8 CTL antigen epitopes appeared 8 mutations in consensus sequence of subtype B and B'. There were no mutations found in the PCR sequences, whereas a few mutations were found in clone sequences (9.80%) in 5 antigen epitopes in p24 region. Eighteen PIs-related mutations and 24 RTIs-related mutations were found in PCR sequences and clone sequences in pol gene region, in which 17 (94.44%) PIs-related mutations and 15 (62.50%) RTIs-related mutations were found only in the clone sequences, respectively. The results showed that the prevalence of HIV-1 drug resistance strains in this study was at a higher level (17.39%), suggesting that some samples were resistant.to existing antiviral drugs.