RESUMEN
BACKGROUND: Increased serum levels of squamous cell carcinoma-related antigen (SCCA) have been observed in patients with allergic disorders, such as atopic dermatitis and bronchial asthma. T(H)2 cytokines, which are known to be involved in the pathogenesis of allergic disorders, stimulate new synthesis of SCCA in cultured human airway epithelial cells. OBJECTIVE: To investigate whether SCCA levels increase during acute exacerbations of asthma in children and whether the T(H)2 cytokines, interleukin 4 (IL-4) and IL-13, are associated with SCCA levels. METHODS: Serum levels of SCCA, IL-4, and IL-13 were measured by enzyme immunoassay during the acute phase of an asthma exacerbation (on hospital admission) and in the recovery phase (after symptoms had subsided). RESULTS: In the 35 children who participated in this study, serum levels of SCCA were significantly elevated in the acute phase (mean +/- SD, 3.09 +/- 2.03 ng/mL) compared with the recovery phase (mean +/- SD, 1.47 +/- 0.64 ng/mL) of an asthma exacerbation (P < .001). In 12 children, the IL-13 levels were observed to correlate with SCCA levels during the recovery phase (r = 0.68, P = .02) but not during the acute phase of an asthma exacerbation. CONCLUSIONS: Serum SCCA levels increase during the acute phase of an asthma exacerbation. During this phase, the increased synthesis of SCCA is not associated with IL-13 but rather mediated by other undefined stimuli. IL-13 may contribute to the basal production of SCCA in asthmatic children.
Asunto(s)
Antígenos de Neoplasias/inmunología , Asma/inmunología , Serpinas/inmunología , Enfermedad Aguda , Adolescente , Antígenos de Neoplasias/sangre , Asma/sangre , Células Cultivadas , Niño , Preescolar , Femenino , Humanos , Lactante , Interferón gamma/inmunología , Interleucina-13/inmunología , Interleucina-4/inmunología , Masculino , Mucosa Respiratoria/inmunología , Serpinas/sangre , Células Th2/inmunologíaRESUMEN
BACKGROUND: Several cytokine combinations have been shown to induce eotaxins in bronchial epithelium. The mechanism for differential regulation of eotaxin expression remains unclear. OBJECTIVE: To investigate the regulatory mechanisms of eotaxin-3 production vs eotaxin-1 production in cultured bronchial epithelium. METHODS: Messenger RNA (mRNA) expression levels of eotaxin-1, eotaxin-2, and eotaxin-3 in a human bronchial epithelial cell line (BEAS-2B) and a normal human bronchial epithelial cell were examined using reverse transcriptase-polymerase chain reaction. Protein production was determined by enzyme-linked immunosorbent assay. Receptor expression was examined by flow cytometry. Phosphorylation of signal transducer and activator of transcription factor 6 (STAT6) was examined by immunoblotting. RESULTS: Eotaxin-1 and eotaxin-3, but not eotaxin-2, mRNA expressions were induced by stimulation with interleukin (IL) 13 or IL-4. However, eotaxin-3 was the only protein detected after stimulation. A consistent 10-fold difference in the potency of IL-13- and IL-4-mediated induction of eotaxin-3 mRNA expression was observed. Interleukin 4 induced more potent induction of STAT6 phosphorylation compared with IL-13. The BEAS-2B cells were observed to express types 1 and 2 IL-4 receptors. Pretreatment with tumor necrosis factor a enhanced IL-4-induced eotaxin-1, but not eotaxin-3, mRNA expression. An inhibitor of nuclear factor-KB inhibited IL-13- and IL-4-induced eotaxin-1 gene expressions. However, it enhanced eotaxin-3 gene expression. CONCLUSIONS: These results suggest that differences in the potency of IL-13- and IL-4-mediated induction of eotaxin-3 might be explained by expression of types 1 and 2 IL-4 receptors in bronchial epithelium. Differences in eotaxin-1 and eotaxin-3 mRNA and protein expression might be due to differential effects of nuclear factor-kappaB on gene expression.
Asunto(s)
Bronquios/citología , Quimiocinas CC/metabolismo , Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Interleucina-13/farmacología , Interleucina-4/farmacología , Células Cultivadas , Quimiocina CCL11 , Quimiocina CCL24 , Quimiocina CCL26 , Quimiocinas CC/genética , Citometría de Flujo , Humanos , Interleucina-13/inmunología , Interleucina-4/inmunología , FN-kappa B/genética , FN-kappa B/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Interleucina-4/metabolismo , Células Th2/inmunologíaRESUMEN
Airway epithelial cells produce a number of chemokines, including eotaxins. Among the three known eotaxins, T helper (Th) type 2 cytokines have been observed to induce the expression of eotaxin-3 mRNA. This study investigated the effect of interferon (IFN)-gamma, a Th1 cytokine, on Th2 cytokine-induced eotaxin-3 production in a bronchial epithelial cell line, BEAS-2B. BEAS-2B cells produced eotaxin-3 after stimulation with the Th2 cytokines interleukin (IL)-13 and IL-4. When BEAS-2B cells were cultured with varying concentrations of IFN-gamma for 24 h, dose-dependent inhibition of Th2 cytokine-induced eotaxin-3 mRNA expression and protein production was observed. This was associated with downregulation of signal transducer and activator of transcription 6 activation. On the other hand, 2-d pretreatment of BEAS-2B cells with IFN-gamma dose-dependently enhanced Th2 cytokine-induced eotaxin-3 mRNA expression and production. IFN-gamma also increased the mRNA expression and protein production of IL-4 receptor (R) alpha in a time- and dose-dependent manner. In addition, IL-2Rgamma, a component of the type 1 IL-4R, was also upregulated by IFN-gamma. These results indicate that IFN-gamma has opposite effects on Th2 cytokine-induced eotaxin-3 production in BEAS-2B cells, depending on the length of exposure. Because high levels of IFN-gamma are produced during viral infection, airway viral infection may affect allergic airway inflammation in vivo by modulation of eotaxin-3 production.
Asunto(s)
Antineoplásicos/farmacología , Quimiocinas CC/metabolismo , Células Epiteliales/metabolismo , Interferón gamma/farmacología , Interleucina-4/farmacología , Receptores de Interleucina-4/metabolismo , Bronquios/citología , Bronquios/metabolismo , Quimiocina CCL26 , Quimiocinas CC/genética , Eosinófilos/metabolismo , Células Epiteliales/citología , Humanos , Interleucina-13/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células TH1/metabolismo , Células Th2/metabolismo , Regulación hacia ArribaRESUMEN
UNLABELLED: A 6-week-old immunocompetent girl developed protein-losing gastroenteropathy (PLGE) and retinitis associated with cytomegalovirus (CMV) infection. At presentation, CMV antigenaemia (6 cells/46,000 white blood cells) and its DNA were detected in the patient's blood and in the mother's milk. Intravenous ganciclovir and gamma-globulin rapidly ameliorated all symptoms and CMV antigenaemia disappeared. No immunological defects were identified in this patient. To the best of our knowledge, this case involves the youngest known immunocompetent patient demonstrating CMV-induced PLGE and retinitis. CONCLUSION: breast-feeding by a cytomegalovirus-positive mother can be a primary cause of early onset cytomegalovirus infection in infants.