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Int. J. Mol. Sci. 2013, 14(12), 24656-24669; doi:10.3390/ijms141224656
Article

Human Interleukin 23 Receptor Induces Cell Apoptosis in Mammalian Cells by Intrinsic Mitochondrial Pathway Associated with the Down-Regulation of RAS/Mitogen-Activated Protein Kinase and Signal Transducers and Activators of Transcription factor 3 Signaling Pathways

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Received: 1 September 2013; in revised form: 5 December 2013 / Accepted: 9 December 2013 / Published: 18 December 2013
(This article belongs to the collection Programmed Cell Death and Apoptosis)
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Abstract: 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.
Keywords: IL-23R; apoptosis; intrinsic pathway; RAS/MAPK; STAT3 IL-23R; apoptosis; intrinsic pathway; RAS/MAPK; STAT3
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Shi, W.-Y.; Che, C.-Y.; Liu, L. Human Interleukin 23 Receptor Induces Cell Apoptosis in Mammalian Cells by Intrinsic Mitochondrial Pathway Associated with the Down-Regulation of RAS/Mitogen-Activated Protein Kinase and Signal Transducers and Activators of Transcription factor 3 Signaling Pathways. Int. J. Mol. Sci. 2013, 14, 24656-24669.

AMA Style

Shi W-Y, Che C-Y, Liu L. Human Interleukin 23 Receptor Induces Cell Apoptosis in Mammalian Cells by Intrinsic Mitochondrial Pathway Associated with the Down-Regulation of RAS/Mitogen-Activated Protein Kinase and Signal Transducers and Activators of Transcription factor 3 Signaling Pathways. International Journal of Molecular Sciences. 2013; 14(12):24656-24669.

Chicago/Turabian Style

Shi, Wei-Ye; Che, Chang-Yan; Liu, Li. 2013. "Human Interleukin 23 Receptor Induces Cell Apoptosis in Mammalian Cells by Intrinsic Mitochondrial Pathway Associated with the Down-Regulation of RAS/Mitogen-Activated Protein Kinase and Signal Transducers and Activators of Transcription factor 3 Signaling Pathways." Int. J. Mol. Sci. 14, no. 12: 24656-24669.


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