RESUMEN
The information conveyed from dendritic cells (DCs) to naïve CD4(+) T cells has crucial influence on their differentiation toward effector T cells. In an effort to identify DC-derived molecules directly contributing to T cell differentiation, we searched for molecules distinctively expressed between two DC subtypes, which were differentiated from peripheral monocytes by cultivation with GM-CSF (for DC1) or IL-3 (for DC2) in the presence of IL-4 and had the ability to induce naïve T cells to differentiate into Th1 or Th2 cells, respectively. As the first step to address this issue, we subtracted DC1 transcripts from those of DC2 and compiled the gene profile dominantly expressed in DC2, whose products are known to reside in other than the nucleus. Intriguingly, many of them were molecules involved in Th2-skewed disease pathologies, such as FN1, ITGAE, GPNMB, PLAUR, FPRL2, LILRB4, SERPINE1, ALOX15, TBXAS1, NCF2, CCL3, IL1RN, SPARC, and STAB1, suggesting that DCs function not only as antigen presenting cells but also as producers of Th2 pathology specific milieus leading to disease deteriorations. We also found that expressions of CYP27A1, PPAP2B, RSAD2, and ABCC3 were up-regulated in DC2, implying their significant function in Th2-deviated states. The identification of differentially expressed genes between DC subtypes provides new insights into their functions and our comparative gene expression profile will be highly useful for the identification of DC-derived key molecules for T cell differentiation.
Asunto(s)
Células Dendríticas/metabolismo , Monocitos/metabolismo , Linfocitos T/metabolismo , Células Th2/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Antígeno B7-2/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Colestanotriol 26-Monooxigenasa/genética , Técnicas de Cocultivo , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Fibronectinas/genética , Perfilación de la Expresión Génica , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Inmunoglobulinas/metabolismo , Cadenas alfa de Integrinas/genética , Interferón gamma/metabolismo , Interleucina-3/farmacología , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Prueba de Cultivo Mixto de Linfocitos , Glicoproteínas de Membrana/metabolismo , Monocitos/citología , Monocitos/efectos de los fármacos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Linfocitos T/citología , Linfocitos T/efectos de los fármacos , Células TH1/citología , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Células Th2/citología , Células Th2/efectos de los fármacos , Antígeno CD83RESUMEN
Beta-amyloid (Abeta) deposition and senile plaque-associated astrocytes are common neuropathological features of Alzheimer's disease (AD). Although the molecular mechanisms by which Abeta contributes to the progression of neuropathologic changes have not been entirely established, there is little doubt that the association of Abeta with astrocytes, the predominant cell type in brain, significantly influences exacerbation of the disease. In an effort to identify astrocyte-derived molecules that may be intimately associated with progression of AD, we identified a novel Abeta-induced rat gene, designated Mib, whose human counterpart covers KIAA0233. Mib-transfected C6 cells express Mib protein in the endoplasmic reticulum and endplasmic reticulum-Golgi-intermediate compartment. To evaluate roles of Mib in AD, we investigated its expression in the AD brain. In non-AD brains, Mib mRNA has been detected in neurons but not in quiescent astrocytes. On the contrary, in AD brains, Mib mRNA is expressed in activated astrocytes associated with senile plaques, but not expressed in neurons around lesions. From these observations, Mib appears to be a novel Abeta-responsive gene that may play a role in astrocyte inflammatory activation around senile plaques in the AD brain.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Astrocitos/metabolismo , Encefalitis/metabolismo , Gliosis/metabolismo , Proteínas de la Membrana/metabolismo , Placa Amiloide/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Animales , Secuencia de Bases , Línea Celular Tumoral , Células Cultivadas , Encefalitis/genética , Encefalitis/fisiopatología , Retículo Endoplásmico/metabolismo , Retículo Endoplásmico/ultraestructura , Regulación de la Expresión Génica/genética , Gliosis/genética , Gliosis/fisiopatología , Aparato de Golgi/metabolismo , Aparato de Golgi/ultraestructura , Humanos , Canales Iónicos , Proteínas de la Membrana/genética , Proteínas de la Membrana/aislamiento & purificación , Datos de Secuencia Molecular , Placa Amiloide/genética , ARN Mensajero/metabolismo , Ratas , Homología de Secuencia de Aminoácido , Activación Transcripcional/genética , Regulación hacia Arriba/genéticaRESUMEN
Lingual epithelial cells, including those of the taste buds, are regularly replaced by proliferative stem cells. We found that integrin beta(1), a keratinocyte stem cell marker, was expressed at the basal layer and taste buds of adult mouse tongue epithelium. We purified and cultured integrin beta(1)-positive cells (termed KT-1 cells), whose growth was stimulated by epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-2). FGF-2 stimulation induced translocation of the FGF type I receptor (FGFR1) into nuclei, suggesting that the growth-stimulating effect of FGF-2 was mediated through FGFR1. EGF and FGF-2 also regulated cell surface expression of the neural cell adhesion molecule (N-CAM) in KT-1 cells. Anti-N-CAM antibody immunoreactivity was restricted to the gustatory epithelium and the nerves in the tongue epithelium, giving rise to the possibility that KT-1 may contain gustatory epithelial cells. KT-1 cells may thus be useful for analyzing the factors that regulate the growth and differentiation of lingual and gustatory epithelial cells in vitro.