Anti-Stat1 (G695) Antikörper (A25359)

The composition of IL-23R complex is similar to that of the IL-12 receptor (IL-12R) complex with a shared IL-12R-β1 chain. The IL-12R-β1 heterodimerizes with IL-23R and IL-12R-β2 to form IL-23R and IL-12R complexes, respectively. The IL-12R-β2 has been shown to function as a tumor suppressor gene and apoptotic inducer. However, whether IL-23R also functions in cell apoptosis is currently unknown. In this study, we demonstrate for the first time that overexpression of IL-23R markedly induces cell apoptosis in both 293ET and HeLa cells. The activations of caspase 3 and caspase 9 are induced by IL-23R. Mechanistic study reveals that IL-23R markedly inhibits RAS/MAPK and STAT3 but not STAT1 and PI-3K/Akt signaling pathways in both 293ET and HeLa cells. Overexpression of IL-23R significantly up-regulates IL-12Rβ1 expression but not IL-23α and IL-12β expressions in both cell lines. Therefore, our data strongly indicates that IL-23R is able to induce cell apoptosis by activating the intrinsic mitochondrial pathways associated with the inhibition in RAS/MAPK and STAT3 activations in mammalian cells.

Cerebral ischemic injury involves a variety of cellular and molecular events. Signal transducers and activators of transcription-1 (STAT-1) activation is associated with neuronal cell death and contributes to ischemic injury. The effects of fludarabine, a specific inhibitor of STAT1 protein, on cerebral ischemic/reperfusion (I/R) injury were studied in a rat model. Rats subjected to I/R injury were either treated with intra-cerebroventricular injection of fludarabine (5,000 μM, 10 μl) or saline 20 min before middle cerebral artery occlusion (MCAO). MR examinations including T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and perfusion-weighted imaging (PWI) were performed after I/R period. Then rat brains were sectioned for triphenyltetrazolium chloride (TTC) stains, analyzed by Western blot and TUNEL staining of apoptosis. It was found that fludarabine treatment decreased the infarct volume of the cerebrum and the number of apoptotic neural cells in the ischemic brain. Compared to saline-treated group, the apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) in the ischemic region were greater, and the mean transit time (MTT) was shortened in the fludarabine-treated group. Moreover, fludarabine inhibited the expression level of phosphorylated STAT1 (P-STAT1) in neural cells after I/R injury, whereas the expression of phosphorylated STAT3 (P-STAT3) was increased. Therefore, we concluded that fludarabine administrated in early stage of cerebral ischemia had neuroprotective effects, and the underlying mechanism could be mediated through inhibiting STAT1 phosphorylation and activating the cross regulation between STAT1 and STAT3 in neural cells.