RESUMEN
Abnormal epithelial repair to damage participates in airway remodeling in asthma by the paracrine regulation of mesenchymal cell functions. Retinoids control epithelial functions through nuclear retinoic acid receptor (RAR) and retinoid X receptor (RXR) activation, yet their expression and contribution to epithelial repair and to airway remodeling in asthma are unknown. We determined the plasma levels of retinol and the immunohistochemical expression of retinoid receptors in damaged and repaired bronchial epithelium from 9 control subjects, 10 subjects with intermittent asthma, 8 subjects with mild-to-moderate asthma, and 8 subjects with severe asthma. In addition, the effect of the retinoid receptor ligands, all-trans-retinoic acid, and 9-cis retinoic acid, on the synthesis of 38 factors potentially involved in epithelial repair and in airway remodeling was determined in human cultured airway epithelial cells and correlated with cell migration and proliferation. Circulating retinol was similar in the three patient groups. In contrast, the epithelial expression of RARgamma, RXRalpha, and RXRgamma was greater in subjects with severe asthma, as compared with patients with milder disease and to control subjects. Retinoid receptor expression correlated positively with the proportion of morphologically intact epithelium. In vitro, retinoids up-regulated the expression of the transcripts encoding transforming growth factor (TGF)-beta1, metalloproteinase-9, beta1-integrin, and hepatocyte growth factor receptor, and promoted wound repair and chemokinesis of human airway epithelial cells without altering proliferation. Cell treatment with an anti-TGF-beta1 monoclonal antibody partially reduced retinoid-induced effects. Persistent interaction between retinoids and some of their receptors, which are overexpressed by the bronchial epithelium of individuals with severe asthma, may contribute to an abnormal repair and to airway remodeling, partly through TGF-beta1 production.
Asunto(s)
Asma/patología , Asma/fisiopatología , Células Epiteliales/metabolismo , Mucosa Nasal/metabolismo , Receptores de Ácido Retinoico/metabolismo , Bronquios/metabolismo , Bronquios/cirugía , Estudios de Casos y Controles , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Inmunohistoquímica , Integrina beta1/metabolismo , Ligandos , Metaloproteinasa 9 de la Matriz/metabolismo , Mucosa Nasal/citología , Mucosa Nasal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-met/metabolismo , ARN Mensajero/metabolismo , Análisis de Regresión , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador beta/metabolismo , Tretinoina/análogos & derivados , Tretinoina/farmacología , Vitamina A/sangre , Cicatrización de Heridas/efectos de los fármacosRESUMEN
RATIONALE: Sarcoidosis is an idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis which involve various organs. Laryngeal involvement is extremely rare, with a prevalence of about 0.5 to 1%. DIAGNOSES: Here we present a case of laryngeal involvement of sarcoidosis demonstrated on F-Fluorodesoxyglucose Positron-Emission Tomography/Computed Tomography (FDG PET/CT). PATIENT CONCERNS: A 63 year-old man suffering from dysphonia was referred to our department for characterization of laryngeal lesion suspicious for cancer with non-informative biopsy, the sample was not sufficient for diagnosis. INTERVENTIONS: FDG PET/CT showed a pathological uptake on the right vocal cord, but also highlighted a bilateral uptake in intrathoracic hilar lymphadenopathy areas, typically found in several inflammatory diseases. OUTCOMES: New laryngeal targeted biopsies revealed non-caseating epithelioid granulomas suggesting sarcoidosis involvement. After 6 months of systemic steroid treatment, FDG PET/CT showed a significant decrease of the laryngeal uptake. LESSONS: This case shows the usefulness of FDG PET/CT to accurately assess inflammatory activity in rare extra-pulmonary sarcoidosis involvement. Moreover, this case emphasizes that FDG PET/CT is an interesting tool for assessing therapeutic efficacy of inflammatory diseases such as sarcoidosis.