RESUMO
We analysed the influence of rhinovirus (RV) in nasopharyngeal fluid (NPF) on type I and III interferon (IFN) responses (e.g. IFN-α and IFN -: λ) and their signal transduction, at baseline and during disease exacerbation, in cohorts of pre-school children with and without asthma.At the time of recruitment into the Europe-wide study PreDicta, and during symptoms, NPF was collected and the local RV colonisation was analysed. Peripheral blood mononuclear cells (PBMCs) were challenged in vitro with RV or not. RNA was analysed by quantitative real-time PCR and gene arrays. Serum was analysed with ELISA for IFNs and C-reactive protein.We found that PBMCs from asthmatic children infected in vitro with the RV1b serotype upregulated MYD88, IRF1, STAT1 and STAT2 mRNA, whereas MYD88, IRF1, STAT1 and IRF9 were predominantly induced in control children. Moreover, during symptomatic visits because of disease exacerbation associated with RV detection in NPF, IFN-α production was found increased, while IFN-λ secretion was already induced by RV in asthmatic children at baseline.During asthma exacerbations associated with RV, asthmatic children can induce IFN-α secretion, indicating a hyperactive immune response to repeated respiratory virus infection.
Assuntos
Asma/imunologia , Proteína C-Reativa/análise , Interferons/sangue , Leucócitos Mononucleares/virologia , Infecções por Picornaviridae/imunologia , Asma/virologia , Células Cultivadas , Pré-Escolar , Progressão da Doença , Europa (Continente) , Feminino , Humanos , Fator Regulador 1 de Interferon/genética , Interferons/imunologia , Masculino , Fator 88 de Diferenciação Mieloide/genética , Nasofaringe/virologia , Estudos Prospectivos , RNA Mensageiro/análise , Rhinovirus , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT2/genética , Transdução de SinaisAssuntos
Asma/etiologia , Asma/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/imunologia , Rhinovirus/imunologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Asma/diagnóstico , Asma/terapia , Modelos Animais de Doenças , Humanos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Camundongos , Infecções por Picornaviridae/virologia , Carga ViralAssuntos
Interferons , Rhinovirus , Antivirais , Asma , Genótipo , Humanos , Infecções por PicornaviridaeRESUMO
Genome-wide association studies (GWAS) associated Family with sequence similarity 13, member A (FAM13A) with non-small cell lung cancer (NSCLC) occurrence. Here, we found increased numbers of FAM13A protein expressing cells in the tumoral region of lung tissues from a cohort of patients with NSCLC. Moreover, FAM13A inversely correlated with CTLA4 but directly correlated with HIF1α levels in the control region of these patients. Consistently, FAM13A RhoGAP was found to be associated with T cell effector molecules like HIF1α and Tbet and was downregulated in immunosuppressive CD4+CD25+Foxp3+CTLA4+ T cells. TGFß, a tumor suppressor factor, as well as siRNA to FAM13A, suppressed both isoforms of FAM13A and inhibited tumor cell proliferation. RNA-Seq analysis confirmed this finding. Moreover, siRNA to FAM13A induced TGFß levels. Finally, in experimental tumor cell migration, FAM13A was induced and TGFß accelerated this process by inducing cell migration, HIF1α, and the FAM13A RhoGAP isoform. Furthermore, siRNA to FAM13A inhibited tumor cell proliferation and induced cell migration without affecting HIF1α. In conclusion, FAM13A is involved in tumor cell proliferation and downstream of TGFß and HIF1α, FAM13A RhoGAP is associated with Th1 gene expression and lung tumor cell migration. These findings identify FAM13A as key regulator of NSCLC growth and progression.