title: Diclofenac inhibits 27-hydroxycholesterol-induced inflammation.
abstract: 27-Hydroxycholesterol (27OHChol) is a cholesterol oxidation product that induces inflammation. In the current study we investigated the effects of diclofenac on inflammatory responses caused by 27OHChol using human monocyte/macrophage (THP-1) cells. Transcription and secretion of CCL2, CCL3, and CCL4 chemokines enhanced by 27OHChol were significantly attenuated by diclofenac in a concentration dependent manner. Migrations of monocytic cells and CCR5-positive Jurkat T cells were reduced proportionally to the concentrations of diclofenac. Superproduction of CCL2 and monocytic cell migration induced by 27OHChol plus LPS were significantly attenuated by diclofenac. Diclofenac also attenuated transcription of MMP-9 and release of its active gene product. These results indicate that diclofenac inhibits 27OHChol-induced inflammatory responses, thereby suppressing inflammation in a milieu rich in cholesterol oxidation products.
authors: Department of Pharmacology, Pusan National University - School of Medicine, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: kimboyoung@pusan.ac.kr.
authors: Bo-Young
authors: BY
authors: Kim
authors: Department of Pharmacology, Pusan National University - School of Medicine, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: squall0211@hanmail.net.
authors: Yonghae
authors: Y
authors: Son
authors: College of Veterinary Medicine and Bio-Safety Research Institute, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea. Electronic address: vetvirus@chonbuk.ac.kr.
authors: Seong-Kug
authors: SK
authors: Eo
authors: Department of Microbiology & Immunology, Pusan National University - School of Medicine, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: ycpark@pusan.ac.kr.
authors: Young Chul
authors: YC
authors: Park
authors: Department of Pharmacology, Pusan National University - School of Medicine, Yangsan, Gyeongnam 50612, Republic of Korea. Electronic address: koanhoi@pusan.ac.kr.
authors: Koanhoi
authors: K
authors: Kim
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D018932:Chemokine CCL2; D004008:Diclofenac / Q000494:pharmacology*; D006801:Humans; D006888:Hydroxycholesterols / Q000633:toxicity*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008024:Ligands; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D006888:Hydroxycholesterols; D008024:Ligands; D019713:Receptors, CCR5; D004008:Diclofenac; C076996:27-hydroxycholesterol; D020780:Matrix Metalloproteinase 9
keywords: 27-Hydroxycholesterol; Diclofenac; Inflammation; Macrophages