title: 15-Deoxy-Δ(12,14)-prostaglandin J(2) attenuates the biological activities of monocyte/macrophage cell lines.
abstract: Monocytes/macrophages link the innate and adaptive immune systems, and in inflammatory disorders their activation leads to tissue damage. 15-Deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), a natural peroxisome proliferator-activated receptor gamma (PPARγ) ligand, has garnered much interest because it possesses anti-inflammatory properties in a number of experimental models. However, whether it regulates monocytes/macrophage pathophysiology is still unknown. This study was designed to examine the effects of 15d-PGJ(2) on the phagocytosis, proliferation and inflammatory cytokines generation in mouse monocyte/macrophage cell line RAW264.7 and J774A.1 cells upon lipopolysaccharide challenge. Our results showed that 15d-PGJ(2) inhibited the phagocytic activity and cell proliferation in a dose-dependent manner, and suppressed proinflammatory cytokines expression, such as tumor necrosis factor-α, transforming growth factor-β1, interleukin-6, and monocyte chemotactic protein-1. These effects were independent of PPARγ, because PPARγ agonist (troglitazone or ciglitazone) and PPARγ antagonist (GW9662) did not affect these activities mentioned above in cells. Treatment of 15d-PGJ(2) also did not modulate expression and distribution of PPARγ. However, these effects of 15d-PGJ(2) were abrogated by antioxidant N-acetylcysteine. Moreover, treatment of 15d-PGJ(2) induced a significant increase in reactive oxygen species production in RAW264.7 and J774A.1 cells. In conclusion, 15d-PGJ(2) attenuates the biological activities of mouse monocyte/macrophage cell line cells involving oxidative stress, independently of PPARγ. These data further underline the anti-inflammation potential of 15d-PGJ(2).
authors.affiliation: Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Changyong
authors.initials: C
authors.lastname: Li
authors.forename: Liying
authors.initials: L
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D010587:Phagocytosis; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C477819:15-deoxyprostaglandin J2; C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D002839:Chromans; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077288:Troglitazone; D015230:Prostaglandin D2; C039671:ciglitazone; D000111:Acetylcysteine