title: CCL5 induces a pro-inflammatory profile in microglia in vitro.
abstract: The chemokine receptors CCR1, CCR2, CCR3, CCR5, and CXCR2 have been found to be expressed on microglia in many neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease. There is emerging evidence that chemokines, besides chemoattraction, might directly modulate reactive profiles of microglia. To address this hypothesis we have investigated the effects of CCL2, CCL3, CCL5, and CXCL1 on cytokine and growth factor production, NO synthesis, and phagocytosis in non-stimulated and lipopolysaccharide-stimulated primary rat microglia. The respective receptors CCR1, CCR5, and CXCR2 were shown to be functionally expressed on microglia. All tested chemokines stimulated chemotaxis whereas only CCL5 increased NO secretion and attenuated IL-10 as well as IGF-1 production in activated microglia. Based on these findings we propose that besides its chemoattractant function CCL5 has a modulatory effect on activated microglia.
authors.affiliation: Department of Neurology, Hannover Medical School, Hannover, Germany.
authors.forename: Jelena
authors.initials: J
authors.lastname: Skuljec
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Refik
authors.initials: R
authors.lastname: Pul
authors.forename: Karelle
authors.initials: K
authors.lastname: Bénardais
authors.forename: Daniela
authors.initials: D
authors.lastname: Ragancokova
authors.forename: Darius
authors.initials: D
authors.lastname: Moharregh-Khiabani
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kotsiari
authors.forename: Corinna
authors.initials: C
authors.lastname: Trebst
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000818:Animals; D001483:Base Sequence; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D017628:Microglia / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054389:Receptors, CCR1 / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: C491766:Ccl2 protein, rat; C515302:Ccr1 protein, rat; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D017931:DNA Primers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D054389:Receptors, CCR1; D023063:Receptors, Interleukin-8B; D011994:Recombinant Proteins; D016753:Interleukin-10; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I