Cited 22 times in
PPARα agonists inhibit inflammatory activation of macrophages through upregulation of β-defensin 1
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이상학 | - |
dc.contributor.author | 강석민 | - |
dc.contributor.author | 김수혁 | - |
dc.contributor.author | 박병희 | - |
dc.contributor.author | 박성하 | - |
dc.contributor.author | 안수진 | - |
dc.date.accessioned | 2016-02-04T11:14:08Z | - |
dc.date.available | 2016-02-04T11:14:08Z | - |
dc.date.issued | 2015 | - |
dc.identifier.issn | 0021-9150 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/139968 | - |
dc.description.abstract | BACKGROUND: Effects of peroxisome proliferator-activated receptor alpha (PPARα) agonists on cardiovascular outcome have been controversial. Although these agents primarily affect lipoprotein metabolism, their pleiotropic anti-inflammatory effect is one of the potential anti-atherosclerotic mechanisms. This study aimed to evaluate the effect of fenofibrate and gemfibrozil on inflammation in macrophages and reveal pathways these agents may affect. METHODS AND RESULTS: The two PPARα agonists inhibited secretion of CXCL2, TNF-α, IL-6, activation of p65 of NF-κB, ERK, and TLR4 expression. These changes occurred simultaneously with upregulation and secretion of β-defensin 1, an inflammation-modulating peptide. To demonstrate the role of β-defensin 1, it was knocked-down by target-specific siRNA. The effects of PPARα agonists on TLR4 expression and chemokine secretion were obviously abrogated with this treatment. In experiments investigating whether β-defensin 1 acts extracellularly, inflammatory chemokines decreased significantly after the addition of recombinant β-defensin 1 or conditioned media to cells. In experiments designed to clarify if the effects of the two agents are PPARα-dependent, induction of mRNA and secretion β-defensin 1 and inhibition of chemokine release were clearly reduced with GW6471, a PPARα blocker. CONCLUSIONS: Our results reveal the pathways by which fenofibrate and gemfibrozil inhibit LPS-induced inflammatory activation of macrophages. This study elucidated a novel anti-inflammatory mechanism that acts through PPARα, β-defensin 1, and TLR4 pathways. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 389~397 | - |
dc.relation.isPartOf | ATHEROSCLEROSIS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Anti-Inflammatory Agents/pharmacology* | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Culture Media, Conditioned/metabolism | - |
dc.subject.MESH | Dose-Response Relationship, Drug | - |
dc.subject.MESH | Fenofibrate/pharmacology* | - |
dc.subject.MESH | Gemfibrozil/pharmacology* | - |
dc.subject.MESH | Inflammation/immunology | - |
dc.subject.MESH | Inflammation/metabolism | - |
dc.subject.MESH | Inflammation/prevention & control* | - |
dc.subject.MESH | Inflammation Mediators/metabolism | - |
dc.subject.MESH | Lipopolysaccharides/pharmacology | - |
dc.subject.MESH | Macrophage Activation/drug effects* | - |
dc.subject.MESH | Macrophages/drug effects* | - |
dc.subject.MESH | Macrophages/immunology | - |
dc.subject.MESH | Macrophages/metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Oxazoles/pharmacology | - |
dc.subject.MESH | PPAR alpha/agonists* | - |
dc.subject.MESH | PPAR alpha/antagonists & inhibitors | - |
dc.subject.MESH | PPAR alpha/metabolism | - |
dc.subject.MESH | RNA Interference | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Toll-Like Receptor 4/metabolism | - |
dc.subject.MESH | Transfection | - |
dc.subject.MESH | Tyrosine/analogs & derivatives | - |
dc.subject.MESH | Tyrosine/pharmacology | - |
dc.subject.MESH | Up-Regulation | - |
dc.subject.MESH | beta-Defensins/genetics | - |
dc.subject.MESH | beta-Defensins/metabolism* | - |
dc.title | PPARα agonists inhibit inflammatory activation of macrophages through upregulation of β-defensin 1 | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학) | - |
dc.contributor.googleauthor | Soo-jin Ann | - |
dc.contributor.googleauthor | Ji Hyung Chung | - |
dc.contributor.googleauthor | Byung Hee Park | - |
dc.contributor.googleauthor | Soo Hyuk Kim | - |
dc.contributor.googleauthor | Jiyoung Jang | - |
dc.contributor.googleauthor | Sungha Park | - |
dc.contributor.googleauthor | Seok-Min Kang | - |
dc.contributor.googleauthor | Sang-Hak Lee | - |
dc.identifier.doi | 10.1016/j.atherosclerosis.2015.04.005 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00037 | - |
dc.contributor.localId | A00640 | - |
dc.contributor.localId | A01479 | - |
dc.contributor.localId | A01512 | - |
dc.contributor.localId | A02243 | - |
dc.contributor.localId | A02833 | - |
dc.relation.journalcode | J00260 | - |
dc.identifier.eissn | 1879-1484 | - |
dc.identifier.pmid | 25881202 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S0021915015002233 | - |
dc.subject.keyword | Atherosclerosis | - |
dc.subject.keyword | Beta-defensins | - |
dc.subject.keyword | Fenofibrate | - |
dc.subject.keyword | Gemfibrozil | - |
dc.subject.keyword | Toll-like receptor 4 | - |
dc.contributor.alternativeName | Lee, Sang Hak | - |
dc.contributor.alternativeName | Kang, Seok Min | - |
dc.contributor.alternativeName | Kim, Soo Hyuk | - |
dc.contributor.alternativeName | Park, Byung Hee | - |
dc.contributor.alternativeName | Park, Sung Ha | - |
dc.contributor.alternativeName | Ann, Soo Jin | - |
dc.contributor.affiliatedAuthor | Kang, Seok Min | - |
dc.contributor.affiliatedAuthor | Kim, Soo Hyuk | - |
dc.contributor.affiliatedAuthor | Park, Byung Hee | - |
dc.contributor.affiliatedAuthor | Park, Sung Ha | - |
dc.contributor.affiliatedAuthor | Ann, Soo Jin | - |
dc.contributor.affiliatedAuthor | Lee, Snag Hak | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 240 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 389 | - |
dc.citation.endPage | 397 | - |
dc.identifier.bibliographicCitation | ATHEROSCLEROSIS, Vol.240(2) : 389-397, 2015 | - |
dc.identifier.rimsid | 49000 | - |
dc.type.rims | ART | - |
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