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15-Deoxy-Δ12,14-prostaglandin J2, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling

Cited 90 time in Web of Science Cited 91 time in Scopus
Authors
Surh, Young-Joon; Na, Hye-Kyung; Park, Jong-Min; Lee, Ha-Na; Kim, Wonki; Yoon, In-Soo; Kim, Dae-Duk
Issue Date
2011-11
Citation
Biochemical Pharmacology, Vol.82 No.10, pp.1335-1351
Keywords
15-deoxy-Delta(12,14)-prostagandin J(2)Cyclopentenone prostaglandinInflammationResolutionAnti-inflammation
Abstract
15-deoxy-Delta(12,14)-prostagandin J(2) (15d-PGJ2) is produced in the inflamed cells and tissues as a consequence of upregulation of cyclooxygenase-2 (COX-2). 15d-PGJ2 is known to be the endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR gamma) with multiple physiological properties. Though one of the terminal products of the COX-2-catalyzed reactions, this cyclopentenone prostaglandin exerts potent anti-inflammatory actions, in part, by antagonizing the activities of pro-inflammatory transcription factors, such as NF-kappa B, STAT3, and AP-1, while stimulating the anti-inflammatory transcription factor Nrf2. These effects are not necessarily dependent on its activation of PPAR gamma, but often involves direct interaction with the above signaling molecules and their regulators. The locally produced 15d-PGJ2 is also involved in the resolution of inflammatory responses. Thus, 15d-PGJ2, especially formed during the late phase of inflammation, might inhibit cytokine secretion and other events by antigen-presenting cells like dendritic cells or macrophages. 15d-PGJ2 can also affect the priming and effector functions of T lymphocytes and induce their apoptotic cell death. These represent a negative feedback explaining how once-initiated immunologic and inflammatory responses are switched off and terminated. In this context, 15d-PGJ2 and its synthetic derivatives have therapeutic potential for the treatment of inflammatory disorders. (C) 2011 Elsevier Inc. All rights reserved.
ISSN
0006-2952
URI
https://hdl.handle.net/10371/172592
DOI
https://doi.org/10.1016/j.bcp.2011.07.100
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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