IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation - PubMed (original) (raw)
IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation
S W Levison et al. Glia. 2000 Dec.
Abstract
Proliferating astrocytes are frequently observed in diseased and injured brains. These newly generated astrocytes are necessary to reestablish the barriers that isolate the CNS from the rest of the body; however, they also create a matrix that inhibits regeneration and remyelination. Therefore, it is important to understand the mechanisms that enable a terminally differentiated astrocyte to reenter the cell cycle. Ciliary neurotrophic factor (CNTF), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), and fibroblastic growth factor-2 (FGF-2) are four cytokines that are rapidly elevated in damaged neural tissue. These cytokines also have been implicated in glial scar formation. We sought to determine whether IL-6 and CNTF stimulate astroglial proliferation alone or in combination with other mitogens. Intraparenchymal CNTF modestly increased the number of proliferating cell nuclear antigen (PCNA) and glial fibrillary acidic protein (GFAP) double positive astrocytes when introduced by stereotactic injection into the adult rat brain. When applied directly to highly enriched rat forebrain astrocyte cultures, neither CNTF nor IL-6-stimulated DNA synthesis. Therefore, they are not astroglial mitogens. However, both cytokines synergized with epidermal growth factor (EGF), increasing its mitogenicity by approximately twofold. Astrocytes that had been "aged" for at least 3 weeks in vitro became refractory to EGF; however, when these "aged" astrocytes were pretreated with either IL-6 or CNTF for as little as 2 h, they became competent to reenter the cell cycle upon exposure to EGF. These data suggest that IL-6 type cytokines, likely by activating STAT family transcription factors, induce the expression of signaling molecules that endow resting astrocytes with the competence to respond to mitogens and to reenter the cell cycle.
Copyright 2000 Wiley-Liss, Inc.
Similar articles
- Ciliary neurotrophic factor activates spinal cord astrocytes, stimulating their production and release of fibroblast growth factor-2, to increase motor neuron survival.
Albrecht PJ, Dahl JP, Stoltzfus OK, Levenson R, Levison SW. Albrecht PJ, et al. Exp Neurol. 2002 Jan;173(1):46-62. doi: 10.1006/exnr.2001.7834. Exp Neurol. 2002. PMID: 11771938 - Ciliary neurotrophic factor stimulates nuclear hypertrophy and increases the GFAP content of cultured astrocytes.
Levison SW, Hudgins SN, Crawford JL. Levison SW, et al. Brain Res. 1998 Aug 24;803(1-2):189-93. doi: 10.1016/s0006-8993(98)00594-0. Brain Res. 1998. PMID: 9729376 - Density dependent modulation of cell cycle protein expression in astrocytes.
Nakatsuji Y, Miller RH. Nakatsuji Y, et al. J Neurosci Res. 2001 Nov 1;66(3):487-96. doi: 10.1002/jnr.1240. J Neurosci Res. 2001. PMID: 11746367 - Cytokines affecting survival and differentiation of an astrocyte progenitor cell line.
Yoshida T, Satoh M, Nakagaito Y, Kuno H, Takeuchi M. Yoshida T, et al. Brain Res Dev Brain Res. 1993 Nov 19;76(1):147-50. doi: 10.1016/0165-3806(93)90132-t. Brain Res Dev Brain Res. 1993. PMID: 8306427 - [Proliferation of neural stem cell and therapy of neuronal degenerative diseases].
Li M, Chen G. Li M, et al. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2004 May;33(3):272-6. doi: 10.3785/j.issn.1008-9292.2004.03.022. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2004. PMID: 15179694 Review. Chinese. No abstract available.
Cited by
- The Role of IL-6 in Neurodegenerative Disorders.
Shan C, Zhang C, Zhang C. Shan C, et al. Neurochem Res. 2024 Apr;49(4):834-846. doi: 10.1007/s11064-023-04085-6. Epub 2024 Jan 16. Neurochem Res. 2024. PMID: 38227113 Review. - Unraveling astrocyte behavior in the space brain: Radiation response of primary astrocytes.
Roggan MD, Kronenberg J, Wollert E, Hoffmann S, Nisar H, Konda B, Diegeler S, Liemersdorf C, Hellweg CE. Roggan MD, et al. Front Public Health. 2023 Apr 6;11:1063250. doi: 10.3389/fpubh.2023.1063250. eCollection 2023. Front Public Health. 2023. PMID: 37089489 Free PMC article. - Crosstalk of Astrocytes and Other Cells during Ischemic Stroke.
He T, Yang GY, Zhang Z. He T, et al. Life (Basel). 2022 Jun 17;12(6):910. doi: 10.3390/life12060910. Life (Basel). 2022. PMID: 35743941 Free PMC article. Review. - Activation and Role of Astrocytes in Ischemic Stroke.
Shen XY, Gao ZK, Han Y, Yuan M, Guo YS, Bi X. Shen XY, et al. Front Cell Neurosci. 2021 Nov 17;15:755955. doi: 10.3389/fncel.2021.755955. eCollection 2021. Front Cell Neurosci. 2021. PMID: 34867201 Free PMC article. Review. - Epidermal Growth Factor in the CNS: A Beguiling Journey from Integrated Cell Biology to Multiple Sclerosis. An Extensive Translational Overview.
Scalabrino G. Scalabrino G. Cell Mol Neurobiol. 2022 May;42(4):891-916. doi: 10.1007/s10571-020-00989-x. Epub 2020 Nov 5. Cell Mol Neurobiol. 2022. PMID: 33151415 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous