Peripheral injection of lipopolysaccharide enhances expression of inflammatory cytokines in murine locus coeruleus: possible role of increased norepinephrine turnover

• Published in: Journal of neurochemistry Vol. 94; no. 2; pp. 393 - 404
• Main Authors: Kaneko, Yoko S., Mori, Keiji, Nakashima, Akira, Sawada, Makoto, Nagatsu, Ikuko, Ota, Akira
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.07.2005; Blackwell; Blackwell Publishing Ltd
• Subjects: Analysis of Variance; Animals; Animals, Newborn; Biological and medical sciences; Carbohydrates; Caspase 1 - metabolism; Cells, Cultured; Cytokines; Cytokines - classification; Cytokines - genetics; Cytokines - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Drug Administration Routes; Drug Interactions; Enzyme-Linked Immunosorbent Assay - methods; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Immunoblotting - methods; Immunohistochemistry - methods; Immunoprecipitation - methods; Inflammation - chemically induced; Inflammation - immunology; inflammatory cytokine; Isolated neuron and nerve. Neuroglia; lipopolysaccharide; Lipopolysaccharides - administration & dosage; locus coeruleus; Locus Coeruleus - drug effects; Locus Coeruleus - metabolism; Male; Medical sciences; Mice; Mice, Inbred C3H; Microglia - drug effects; Nervous system; Neurology; norepinephrine; Norepinephrine - metabolism; Reverse Transcriptase Polymerase Chain Reaction - methods; Ribonucleic acid; RNA; RNA, Messenger - biosynthesis; Rodents; Time Factors; Vertebrates: nervous system and sense organs; Neuroglia; Rodentia; Cytokine; Central nervous system; Homeostasis; Interleukin 1β; Male; Catecholamine; Gene expression; Encephalon; Microglia; Vertebrata; inflammatory cytokine; Mammalia; Mouse; Tumor necrosis factor; Lipopolysaccharide; Norepinephrine; Locus coeruleus
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03209.x

Cytokines and catecholamines are known to constitute a significant portion of the regulatory neuroimmune networks involved in maintaining homeostasis in the central nervous system (CNS). Although we have already reported an increase in norepinephrine (NE) turnover within the locus coeruleus (LC) at 2 and 4 h after the intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), the implication of this increase remains unclear. In view of evidence that norepinephrine (NE) acts in an anti‐inflammatory manner by way of negatively regulating pro‐inflammatory cytokine expression, we examined the inflammatory cytokine expression levels in the LC of C3H/HeN mice (male, 8 weeks old) after an i.p. LPS injection. The mRNA expression levels of the genes encoding IL‐1β and TNF‐α within the LC increased during the first 2 h, and showed two peaks, the first at 4 h and the second lesser one at 15 h after the LPS injection. Microglia, which are one of the major cell types that produce pro‐inflammatory cytokines in the CNS, were isolated from mouse neonate brains in order to clarify more precisely the relationship between the changes in NE content and the up‐regulation of inflammatory cytokines in the LC. Simultaneous incubation of microglia with LPS and NE enhanced the expression of IL‐1β at both mRNA and protein levels, but reduced the mRNA and protein levels of TNF‐α. These data support the hypothesis that NE negatively regulates the expression of pro‐inflammatory cytokine expression, at least in the case of TNF‐α, which action could contribute to the observed anti‐inflammatory properties of NE. This report, based on the results of both in vivo and in vitro experiments, is the first to suggest a relationship between NE content and cytokine expression levels in the CNS.