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Met5‐enkephalin‐Arg6‐Phe7 (MEAP) attenuates pro‐inflammatory responses in human epicardial adipocytes
Author(s) -
Stoll Lynn L,
Denning Gerene M,
Ackermann Laynez W,
Weintraub Neal L,
Dickson Eric W
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a769-c
Subject(s) - proinflammatory cytokine , cd14 , endogeny , coronary arteries , adipose tissue , medicine , enkephalin , inflammation , coronary artery disease , endocrinology , artery , opioid , receptor
Adipocytes are previously unrecognized sources of proinflammatory mediators that contribute to metabolic syndrome, diabetes, and atherosclerosis. Epicardial fat overlying coronary arteries produces higher levels of inflammatory mediators than subcutaneous fat. Because of their unique properties and location, we hypothesize that epicardial adipocytes (EpAd) may play an important role in transducing inflammatory responses to coronary arteries. Enkephalins are naturally occurring endogenous delta opioids that improve myocardial ischemic tolerance. We found that EpAd express CD14, which plays a crucial role in transducing signaling by endotoxin and other inflammatory mediators, and release significant levels of IL‐8 in response to both endotoxin and TNF‐alpha. Met5‐enkephalin‐Arg6‐Phe7 (MEAP; 1 μM) inhibited this IL‐8 release by 50% or more, as did PCP‐enkephalin. Microarray analysis revealed that MEAP blocked LPS‐induced expression of a number of immunomodulatory genes. Together, these data suggest that EpAd may contribute to proinflammatory responses in coronary arteries, and that endogenous enkephalins may blunt these effects, thus playing a protective role in coronary artery disease.