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IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways.
J Neurosci Res 2006; 84(5):1037-46JN

Abstract

In the present study we sought to examine cell-cell interactions by investigating the effects of factors released by stimulated microglia on inducible nitric oxide (NO) synthase (iNOS) induction in astrocytoma cells. After examining the temporal profiles of proinflammatory molecules induced by lipopolysaccharide (LPS) stimulation in BV2 microglial cells, iNOS and IL-1beta were observed to be the first immediate-response molecules. Removal of LPS after 3 hr stimulation abrogated NO release, whereas a full induction of IL-1beta was retained in BV2 cells. We observed consistently that conditioned medium (CM) from activated microglia resulted in the induction of iNOS in C6 cells, and IL-1beta was shown to be a key regulator of iNOS induction. An IL-1beta-neutralizing antibody diminished NO induction. Incubation with recombinant IL-1beta stimulated NO release to a lesser extent compared to microglial CM; co-treatment of LPS and IL-1beta had a potent, synergistic effect on NO release from C6 cells. Transient transfection with MEK kinase 1 (MEKK1) or nuclear factor-kappa B (NF-kappaB) expression plasmids induced iNOS, and IL-1beta further enhanced the MEKK1 response. Furthermore, IL-1beta-mediated NO release from C6 cells was significantly suppressed by inhibition of p38 mitogen activated protein kinase (MAPK) or NF-kappaB by specific chemical inhibitors. Both IL-1beta and MEKK1 stimulated p38 and JNK MAPKs, as well as the NF-kappaB pathway, to induce iNOS in C6 cells. Microglia may represent an anti-tumor response in the central nervous system, which is potentiated by the local secretion of immunomodulatory factors that in turn affects astrocytoma (glioma) cells. A better understanding of microglia-glioma or microglia-astrocyte interactions will help in the design of novel immune-based therapies for brain tumors or neuronal diseases.

Authors+Show Affiliations

Department of Physiology and Biophysics, and Center for Advanced Medical Education by BK21 Project, Inha University, College of Medicine, Incheon, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16881054

Citation

Kim, Yun-Jung, et al. "IL-1beta, an Immediate Early Protein Secreted By Activated Microglia, Induces iNOS/NO in C6 Astrocytoma Cells Through P38 MAPK and NF-kappaB Pathways." Journal of Neuroscience Research, vol. 84, no. 5, 2006, pp. 1037-46.
Kim YJ, Hwang SY, Oh ES, et al. IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways. J Neurosci Res. 2006;84(5):1037-46.
Kim, Y. J., Hwang, S. Y., Oh, E. S., Oh, S., & Han, I. O. (2006). IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways. Journal of Neuroscience Research, 84(5), pp. 1037-46.
Kim YJ, et al. IL-1beta, an Immediate Early Protein Secreted By Activated Microglia, Induces iNOS/NO in C6 Astrocytoma Cells Through P38 MAPK and NF-kappaB Pathways. J Neurosci Res. 2006;84(5):1037-46. PubMed PMID: 16881054.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways. AU - Kim,Yun-Jung, AU - Hwang,So-Young, AU - Oh,Eok-Soo, AU - Oh,Seikwan, AU - Han,Inn-Oc, PY - 2006/8/2/pubmed PY - 2006/12/9/medline PY - 2006/8/2/entrez SP - 1037 EP - 46 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 84 IS - 5 N2 - In the present study we sought to examine cell-cell interactions by investigating the effects of factors released by stimulated microglia on inducible nitric oxide (NO) synthase (iNOS) induction in astrocytoma cells. After examining the temporal profiles of proinflammatory molecules induced by lipopolysaccharide (LPS) stimulation in BV2 microglial cells, iNOS and IL-1beta were observed to be the first immediate-response molecules. Removal of LPS after 3 hr stimulation abrogated NO release, whereas a full induction of IL-1beta was retained in BV2 cells. We observed consistently that conditioned medium (CM) from activated microglia resulted in the induction of iNOS in C6 cells, and IL-1beta was shown to be a key regulator of iNOS induction. An IL-1beta-neutralizing antibody diminished NO induction. Incubation with recombinant IL-1beta stimulated NO release to a lesser extent compared to microglial CM; co-treatment of LPS and IL-1beta had a potent, synergistic effect on NO release from C6 cells. Transient transfection with MEK kinase 1 (MEKK1) or nuclear factor-kappa B (NF-kappaB) expression plasmids induced iNOS, and IL-1beta further enhanced the MEKK1 response. Furthermore, IL-1beta-mediated NO release from C6 cells was significantly suppressed by inhibition of p38 mitogen activated protein kinase (MAPK) or NF-kappaB by specific chemical inhibitors. Both IL-1beta and MEKK1 stimulated p38 and JNK MAPKs, as well as the NF-kappaB pathway, to induce iNOS in C6 cells. Microglia may represent an anti-tumor response in the central nervous system, which is potentiated by the local secretion of immunomodulatory factors that in turn affects astrocytoma (glioma) cells. A better understanding of microglia-glioma or microglia-astrocyte interactions will help in the design of novel immune-based therapies for brain tumors or neuronal diseases. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/16881054/IL_1beta_an_immediate_early_protein_secreted_by_activated_microglia_induces_iNOS/NO_in_C6_astrocytoma_cells_through_p38_MAPK_and_NF_kappaB_pathways_ L2 - https://doi.org/10.1002/jnr.21011 DB - PRIME DP - Unbound Medicine ER -