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Lipopolysaccharide and proinflammatory cytokines require different astrocyte states to induce nitric oxide production.
J Neurosci Res. 2005 Dec 01; 82(5):717-28.JN

Abstract

Nitric oxide (NO) production by astrocytes is a significant factor affecting brain physiology and pathology, but the mechanism by which it is regulated is not known. Previous studies using different specimens and stimuli might have described different aspects of a complex system. We investigated the effect of culture and stimulus conditions on NO production by cultured astrocytes and identified two combinations of these allowing NO production. Lipopolysaccharide (LPS)-induced NO production required a high seeding cell density and was independent of the serum concentration, whereas that induced by proinflammatory cytokines required simultaneous treatment with interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma and low-serum conditions but was less affected by the seeding density. These two pathways showed differential sensitivity to protein kinase inhibitors. Both LPS and cytokines induced expression of inducible nitric oxide synthase (iNOS). Although LPS-induced iNOS expression required a high seeding cell density, cytokine-induced iNOS expression, in contrast to NO production, was not affected by the serum concentration. These results suggest that astrocytes interact with the environment and alter their responsiveness to NO production-inducing stimuli by regulating iNOS expression and activity. This is the first evidence for the selective use of two different regulatory pathways in any cell type.

Authors+Show Affiliations

Laboratory of Cellular Neurobiology, School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.No 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

16247808

Citation

Kozuka, Nagisa, et al. "Lipopolysaccharide and Proinflammatory Cytokines Require Different Astrocyte States to Induce Nitric Oxide Production." Journal of Neuroscience Research, vol. 82, no. 5, 2005, pp. 717-28.
Kozuka N, Itofusa R, Kudo Y, et al. Lipopolysaccharide and proinflammatory cytokines require different astrocyte states to induce nitric oxide production. J Neurosci Res. 2005;82(5):717-28.
Kozuka, N., Itofusa, R., Kudo, Y., & Morita, M. (2005). Lipopolysaccharide and proinflammatory cytokines require different astrocyte states to induce nitric oxide production. Journal of Neuroscience Research, 82(5), 717-28.
Kozuka N, et al. Lipopolysaccharide and Proinflammatory Cytokines Require Different Astrocyte States to Induce Nitric Oxide Production. J Neurosci Res. 2005 Dec 1;82(5):717-28. PubMed PMID: 16247808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipopolysaccharide and proinflammatory cytokines require different astrocyte states to induce nitric oxide production. AU - Kozuka,Nagisa, AU - Itofusa,Rurika, AU - Kudo,Yoshihisa, AU - Morita,Mitsuhiro, PY - 2005/10/26/pubmed PY - 2006/4/29/medline PY - 2005/10/26/entrez SP - 717 EP - 28 JF - Journal of neuroscience research JO - J Neurosci Res VL - 82 IS - 5 N2 - Nitric oxide (NO) production by astrocytes is a significant factor affecting brain physiology and pathology, but the mechanism by which it is regulated is not known. Previous studies using different specimens and stimuli might have described different aspects of a complex system. We investigated the effect of culture and stimulus conditions on NO production by cultured astrocytes and identified two combinations of these allowing NO production. Lipopolysaccharide (LPS)-induced NO production required a high seeding cell density and was independent of the serum concentration, whereas that induced by proinflammatory cytokines required simultaneous treatment with interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma and low-serum conditions but was less affected by the seeding density. These two pathways showed differential sensitivity to protein kinase inhibitors. Both LPS and cytokines induced expression of inducible nitric oxide synthase (iNOS). Although LPS-induced iNOS expression required a high seeding cell density, cytokine-induced iNOS expression, in contrast to NO production, was not affected by the serum concentration. These results suggest that astrocytes interact with the environment and alter their responsiveness to NO production-inducing stimuli by regulating iNOS expression and activity. This is the first evidence for the selective use of two different regulatory pathways in any cell type. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/16247808/Lipopolysaccharide_and_proinflammatory_cytokines_require_different_astrocyte_states_to_induce_nitric_oxide_production_ L2 - https://doi.org/10.1002/jnr.20671 DB - PRIME DP - Unbound Medicine ER -