title: CXCL5 limits macrophage foam cell formation in atherosclerosis.
abstract: The ELR(+)-CXCL chemokines have been described typically as potent chemoattractants and activators of neutrophils during the acute phase of inflammation. Their role in atherosclerosis, a chronic inflammatory vascular disease, has been largely unexplored. Using a mouse model of atherosclerosis, we found that CXCL5 expression was upregulated during disease progression, both locally and systemically, but was not associated with neutrophil infiltration. Unexpectedly, inhibition of CXCL5 was not beneficial but rather induced a significant macrophage foam cell accumulation in murine atherosclerotic plaques. Additionally, we demonstrated that CXCL5 modulated macrophage activation, increased expression of the cholesterol efflux regulatory protein ABCA1, and enhanced cholesterol efflux activity in macrophages. These findings reveal a protective role for CXCL5, in the context of atherosclerosis, centered on the regulation of macrophage foam cell formation.
authors: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors: Anthony
authors: A
authors: Rousselle
authors: Fatimunnisa
authors: F
authors: Qadri
authors: Lisa
authors: L
authors: Leukel
authors: Rüstem
authors: R
authors: Yilmaz
authors: Jean-Fred
authors: JF
authors: Fontaine
authors: Gabin
authors: G
authors: Sihn
authors: Michael
authors: M
authors: Bader
authors: Amrita
authors: A
authors: Ahluwalia
authors: Johan
authors: J
authors: Duchene
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000276:immunology*; D054365:Chemokine CXCL5 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005487:Foam Cells / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D001057:Apolipoproteins E; D054365:Chemokine CXCL5; C094739:Cxcl5 protein, mouse; D012333:RNA, Messenger; D023063:Receptors, Interleukin-8B; D002784:Cholesterol
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