RESUMEN
Cell penetrating peptide derived from human eosinophil cationic protein (CPPecp) is a 10-amino-acid peptide containing a core heparan sulfate (HS)-binding motif of human eosinophil cationic protein (ECP). It binds and penetrates bronchial epithelial cells without cytotoxic effects. Here we investigated airway-protective effects of CPPecp in BEAS-2B cell line and mite-induced airway allergic inflammation in BALB/c mice. In BEAS-2B cell, CPPecp decreases ECP-induced eotaxin mRNA expression. CPPecp also decreases eotaxin secretion and p-STAT6 activation induced by ECP, as well as by IL-4. In vivo studies showed CPPecp decreased mite-induced airway inflammation in terms of eosinophil and neutrophil count in broncho-alveolar lavage fluid, peri-bronchiolar and alveolar pathology scores, cytokine production in lung protein extract including interleukin (IL)-5, IL-13, IL-17A/F, eotaxin; and pause enhancement from methacholine stimulation. CPPecp treated groups also showed lower serum mite-specific IgE level. In this study, we have demonstrated the in vitro and in vivo anti-asthma effects of CPPecp.
Asunto(s)
Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Péptidos de Penetración Celular/farmacología , Proteína Catiónica del Eosinófilo/química , Mucosa Respiratoria/efectos de los fármacos , Alérgenos/inmunología , Animales , Antiasmáticos/uso terapéutico , Antígenos Dermatofagoides/inmunología , Asma/inmunología , Asma/patología , Bronquios/citología , Bronquios/efectos de los fármacos , Bronquios/inmunología , Línea Celular , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/uso terapéutico , Citocinas/inmunología , Citocinas/metabolismo , Evaluación Preclínica de Medicamentos , Eosinófilos/inmunología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Neutrófilos/inmunología , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Mucosa Respiratoria/citología , Mucosa Respiratoria/inmunología , Resultado del TratamientoRESUMEN
We report a rare case of diffuse systemic sclerosis (SSc) evolving into diffuse SSc/systemic lupus erythematosus (SLE) overlap syndrome. A 15-year-old boy was diagnosed as diffuse SSc with initial presentations of Raynaud's phenomenon and skin tightening. He underwent Chinese herbal treatment and clinical symptoms deteriorated in the following 3 years. On admission to our ward, serositis with pleural effusion, severe pulmonary fibrosis with moderate pulmonary hypertension, swallowing difficulty, and polyarthritis were observed. Autoantibody profiles revealed concurrence of anti-double-stranded DNA, anti-Smith, anti-topoisomerase I, and anti-ribonucleoprotein antibodies. The patient fulfills the criteria for both diffuse SSc and SLE. After drainage for pleural effusion accompanied by oral prednisolone and sildenafil, there were improvement of respiratory distress, swallowing difficulty, and pulmonary hypertension. In conclusion, connective tissue diseases may overlap with each other during the disease course. Serial follow-up for clinical symptoms as well as serological changes is recommended.