title: Functional expression of CCL6 by rat microglia: a possible role of CCL6 in cell-cell communication.
abstract: There is growing evidence that chemokines play important roles in the immune surveillance of central nervous system (CNS). In the CNS, microglia are primary immune effector cells and secrete various chemokines in response to their microenvironment. Using the RT-PCR procedure and indirect immunofluorescence analysis, we found that CCL6 (known as C10/MRP-1 in mouse) was expressed in rat primary microglia without any stimulation, but not in primary astrocytes, although both cell types expressed CCR1 mRNA, which is a receptor for CCL6. Furthermore, immunohistochemical analysis demonstrated that microglia produced CCL6 protein in a normal brain, suggesting that microglia may be the primary source of CCL6 in a normal brain. Recombinant rat CCL6 mediated the migration of microglia and astrocytes in vitro. The CCL6-mediated cell migration was blocked by treating the cells with LY294002, a PI3-kinase inhibitor and Western blot analysis showed that the phosphorylation of Akt could be induced by treating microglia with a recombinant CCL6, suggesting that CCL6 functions by activating the PI3-kinase/Akt pathway. A proinflammatory cytokine, interferon-gamma enhanced the expression of both CCL6 mRNA and protein in microglia, while other proinflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha and an anti-inflammatory cytokine, transforming growth factor-beta exerted no effect on CCL6 expression in microglia. These findings suggest that CCL6 may be a mediator released by microglia for cell-cell communication under physiological as well as pathological conditions of CNS.
authors.affiliation: Division of Molecular and Cellular Physiology, Department of Molecular and Cellular Biology, School of Medicine, Ehime University, Toon City, Ehime 791-0295, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Kanno
authors.forename: Shunji
authors.initials: S
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Akiko
authors.initials: A
authors.lastname: Yokoyama
authors.forename: Aiko
authors.initials: A
authors.lastname: Sakamoto
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Imai
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002450:Cell Communication / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology; D002867:Chromones / Q000494:pharmacology; D003001:Cloning, Molecular / Q000379:methods; D016207:Cytokines / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D016548:Prosencephalon / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019742:Chemokines, CC; D002867:Chromones; D016207:Cytokines; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D037102:Lectins; D009025:Morpholines; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D007371:Interferon-gamma