title: 27-Oxygenated cholesterol induces expression of CXCL8 in macrophages via NF-κB and CD88.
abstract: We attempted to determine the effects of a milieu rich in cholesterol molecules on expression of chemokine CXCL8. A high-cholesterol diet led to an increased transcription of the IL-8 gene in the arteries and elevated levels of CXCL8 in sera of ApoE(-/-) mice, compared with those of wild-type C57BL/6 mice. Treatment of THP-1 monocyte/macrophage cells with 27-hydroxycholesterol (27OHChol) resulted in transcription of the IL-8 gene and increased secretion of its corresponding gene product whereas cholesterol did not induce expression of CXCL8 in THP-1 cells. 27OHChol-induced transcription of the IL-8 gene was blocked by cycloheximide, but not by polymyxin B. Treatment of THP-1 cells with 27OHChol caused translocation of p65 NF-κB subunit into the nucleus and up-regulation of CD88. Inhibition of NF-κB and CD88 using SN50 and W-54011, respectively, resulted in reduced transcription of the IL-8 gene and attenuated secretion of CXCL8 induced by 27OHChol. We propose that oxidatively modified cholesterol like 27OHChol, rather than cholesterol, is responsible for sustained expression of CXCL8 in monocytes/macrophages in atherosclerotic arteries.
authors.affiliation: Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea. Electronic address: lala1647@hanmail.net.
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Pusan National University Hospital, Pusan 602-739, Republic of Korea. Electronic address: vasculardoctorlee@gmail.com.
authors.forename: Chung Won
authors.initials: CW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea. Electronic address: kimboyoung@pusan.ac.kr.
authors.forename: Bo-Young
authors.initials: BY
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea. Electronic address: youngjung@pusan.ac.kr.
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan, Jeonbuk 570-752, Republic of Korea. Electronic address: vetvirus@chonbuk.ac.kr.
authors.forename: Seong-Kug
authors.initials: SK
authors.lastname: Eo
authors.affiliation: Department of Microbiology & Immunology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea. Electronic address: ycpark@pusan.ac.kr.
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Pusan National University, School of Medicine, Yangsan, Gyeongnam 626-870, Republic of Korea. Electronic address: koanhoi@pusan.ac.kr.
authors.forename: Koanhoi
authors.initials: K
authors.lastname: Kim
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D050197:Atherosclerosis / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D006888:Hydroxycholesterols / Q000737:chemistry / Q000494:pharmacology*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D006888:Hydroxycholesterols; D016209:Interleukin-8; D016328:NF-kappa B; D044087:Receptor, Anaphylatoxin C5a; C076996:27-hydroxycholesterol
keywords: 27-Hydroxycholesterol; Atherosclerosis; CD88; CXCL8; Macrophages; NF-κB