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Mechanisms of interleukin-1beta-induced GDNF release from rat glioma cells.
Brain Res. 2009 Jun 05; 1274:11-20.BR

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is highly expressed both in neurons and astrocytes in injured tissues. Astrocytes support neurons by releasing neurotrophic factors including GDNF. It has been reported that various agents including cytokines such as interleukin (IL)-1beta induce GDNF mRNA expression and the release in astrocytes. However, the mechanism behind the GDNF synthesis and release remains unclear. Herein, we investigated the mechanisms of the IL-1beta-induced GDNF release from rat C6 glioma cells. IL-1beta time dependently stimulated GDNF release from C6 cells. IL-1beta induced the phosphorylation of inhibitor kappa B (IkappaB), p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and signal transducer and activator of transcription (STAT) 3. The IL-1beta-stimulated levels of GDNF were suppressed by wedelolactone, an inhibitor of IkappaB kinase, SB203580, an inhibitor of p38 MAP kinase, PD98059, an inhibitor of MAP kinase kinase 1/2 or Janus family of tyrosine kinase (JAK) inhibitor I, an inhibitor of upstream kinase of STAT3. On the contrary, SP600125, an inhibitor of SAPK/JNK, failed to reduce the IL-1beta-effect. These results strongly suggest that IL-1beta stimulates GDNF release through the pathways of IkappaB-nuclear factor kappa B, p38 MAP kinase, p44/p42 MAP kinase and JAK-STAT3, but not through the SAPK/JNK pathway in glioma cells.

Authors+Show Affiliations

Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. kumiko-t@m2.gyao.ne.jpNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19362079

Citation

Tanabe, Kumiko, et al. "Mechanisms of Interleukin-1beta-induced GDNF Release From Rat Glioma Cells." Brain Research, vol. 1274, 2009, pp. 11-20.
Tanabe K, Nishimura K, Dohi S, et al. Mechanisms of interleukin-1beta-induced GDNF release from rat glioma cells. Brain Res. 2009;1274:11-20.
Tanabe, K., Nishimura, K., Dohi, S., & Kozawa, O. (2009). Mechanisms of interleukin-1beta-induced GDNF release from rat glioma cells. Brain Research, 1274, 11-20. https://doi.org/10.1016/j.brainres.2009.03.063
Tanabe K, et al. Mechanisms of Interleukin-1beta-induced GDNF Release From Rat Glioma Cells. Brain Res. 2009 Jun 5;1274:11-20. PubMed PMID: 19362079.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanisms of interleukin-1beta-induced GDNF release from rat glioma cells. AU - Tanabe,Kumiko, AU - Nishimura,Kazumi, AU - Dohi,Shuji, AU - Kozawa,Osamu, Y1 - 2009/04/09/ PY - 2009/01/02/received PY - 2009/03/26/revised PY - 2009/03/31/accepted PY - 2009/4/14/entrez PY - 2009/4/14/pubmed PY - 2009/7/30/medline SP - 11 EP - 20 JF - Brain research JO - Brain Res VL - 1274 N2 - Glial cell line-derived neurotrophic factor (GDNF) is highly expressed both in neurons and astrocytes in injured tissues. Astrocytes support neurons by releasing neurotrophic factors including GDNF. It has been reported that various agents including cytokines such as interleukin (IL)-1beta induce GDNF mRNA expression and the release in astrocytes. However, the mechanism behind the GDNF synthesis and release remains unclear. Herein, we investigated the mechanisms of the IL-1beta-induced GDNF release from rat C6 glioma cells. IL-1beta time dependently stimulated GDNF release from C6 cells. IL-1beta induced the phosphorylation of inhibitor kappa B (IkappaB), p38 mitogen-activated protein (MAP) kinase, p44/p42 MAP kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and signal transducer and activator of transcription (STAT) 3. The IL-1beta-stimulated levels of GDNF were suppressed by wedelolactone, an inhibitor of IkappaB kinase, SB203580, an inhibitor of p38 MAP kinase, PD98059, an inhibitor of MAP kinase kinase 1/2 or Janus family of tyrosine kinase (JAK) inhibitor I, an inhibitor of upstream kinase of STAT3. On the contrary, SP600125, an inhibitor of SAPK/JNK, failed to reduce the IL-1beta-effect. These results strongly suggest that IL-1beta stimulates GDNF release through the pathways of IkappaB-nuclear factor kappa B, p38 MAP kinase, p44/p42 MAP kinase and JAK-STAT3, but not through the SAPK/JNK pathway in glioma cells. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/19362079/Mechanisms_of_interleukin_1beta_induced_GDNF_release_from_rat_glioma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(09)00687-8 DB - PRIME DP - Unbound Medicine ER -