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RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytes
Author(s) -
Luo Yi,
Berman Michael A.,
Zhai Qiwei,
Fischer Falko R.,
AbromsonLeeman Sara R.,
Zhang Ye,
Kuziel William A.,
Gerard Craig,
Dorf Martin E.
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10079
Subject(s) - ccr1 , chemokine , astrocyte , biology , chemokine receptor , microbiology and biotechnology , ccl13 , ccl3 , macrophage inflammatory protein , cx3cr1 , ccl7 , cc chemokine receptors , neuroglia , immunology , inflammation , neuroscience , ccl2 , central nervous system
Abstract Cultured mouse astrocytes respond to the CC chemokine RANTES by production of chemokine and cytokine transcripts. Stimulation of astrocytes with 1 nM RANTES or 3–10 nM of the structurally related chemokines (eotaxin, macrophage inflammatory protein‐1α and ‐β [MIP‐1α, MIP‐1β]) induced transcripts for KC, monocyte chemoattractant protein‐1 (MCP‐1), tumor necrosis factor‐α (TNF‐α), MIP‐1α, MIP‐2, and RANTES in a chemokine and cell‐specific fashion. Synthesis of chemokine (KC and MCP‐1) and cytokine (TNF‐α) proteins was also demonstrated. RANTES‐mediated chemokine synthesis was specifically inhibited by pertussis toxin, indicating that G‐protein‐coupled chemokine receptors participated in astrocyte signaling. Astrocytes expressed CCR1 and CCR5 (the redundant RANTES receptors). Astrocytes derived from mice with targeted mutations of either CCR1 or CCR5 respond after RANTES stimulation, suggesting multiple chemokine receptors may separately mediate RANTES responsiveness in astrocytes. Preliminary data suggest activation of the MAP kinase pathway is also critical for RANTES‐mediated signaling in astrocytes. Treatment with RANTES specifically modulated astrocyte receptors upregulating intercellular adhesion molecule 1 (ICAM‐1) and downregulating CX3CR1 expression. Thus, after chemokine treatment, astrocytes release proinflammatory mediators and reprogram their surface molecules. The combined effects of RANTES may serve to amplify inflammatory responses within the central nervous system. GLIA 39:19–30, 2002. © 2002 Wiley‐Liss, Inc.