RESUMEN
Endoplasmic reticulum (ER) stress has recently been implicated in human diseases such as Alzheimer׳s disease (AD) and Parkinson׳s disease (PD). However, the link between the immune system, ER stress, and the development of neurodegenerative diseases has not yet been clarified in detail. Mouse primary cultured astrocytes were treated with lipopolysaccharide (LPS) and/or tunicamycin (Tm), and inducible nitric oxide synthase (iNOS) and interleukin (IL)-1ß levels were then measured using RT-PCR, ELISA, and Western blotting. Activation of the immune system by LPS triggered inflammatory responses in astrocytes, as measured by the induction of iNOS and IL-1ß. Tm-induced ER stress inhibited the LPS-induced expression of IL-1ß and iNOS at the protein level. On the other hand, ER stress alone did not induce the expression of IL-1ß or iNOS. The inhibitory effect of ER stress on iNOS and IL-1ß may not be mediated transcriptionally as we did not observe inhibition at the mRNA level. LPS-induced iNOS protein levels were attenuated by the Tm post-treatment in the absence of LPS. Overall, these results suggest that ER stress negatively regulates the expression of IL-1ß and iNOS in LPS-activated astrocytes.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Neuroglía/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Tunicamicina/farmacología , Animales , Animales Recién Nacidos , Encéfalo/citología , Brefeldino A/farmacología , Células Cultivadas , Quelantes/farmacología , Interacciones Farmacológicas , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Interleucina-1beta/genética , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/genética , Inhibidores de la Síntesis de la Proteína/farmacología , Factores de Tiempo , Factor de Transcripción CHOP/metabolismoRESUMEN
The disruption of endoplasmic reticulum (ER) function can lead to neurodegenerative disorders, in which inflammation has also been implicated. We investigated the possible correlation between ER stress and immune function using glial cells. We demonstrated that ER stress synergistically enhanced prostaglandin (PG) E2 + interferon (IFN) γ-induced interleukin (IL)-6 production. This effect was mediated through cAMP. Immune-activated glial cells produced inducible nitric oxide synthase (iNOS). Interestingly, ER stress inhibited PGE2 + IFNγ-induced iNOS expression. Similar results were obtained when cells were treated with dbcAMP + IFNγ. Thus, cAMP has a dual effect on immune reactions; cAMP up-regulated IL-6 expression, but down-regulated iNOS expression under ER stress. Therefore, our results suggest a link between ER stress and immune reactions in neurodegenerative diseases.
