title: Effect of prostaglandin I2 analogs on macrophage inflammatory protein 1α in human monocytes via I prostanoid receptor and cyclic adenosine monophosphate.
abstract: OBJECTIVE
  Inflammation plays critical roles in atherosclerosis. Chemokines are responsible for leukocyte trafficking and involve in inflammatory diseases. Macrophage inflammatory protein 1α (MIP-1α) has been implicated in atherosclerotic lesion formation. Prostaglandin I2 (PGI2) analog, used in pulmonary hypertension, has been reported to have anti-inflammatory functions. However, little is known about its role in the MIP-1α production in human monocytes.
  
  
  METHODS
  We investigated the effects of 3 conventional (iloprost, beraprost, and treprostinil) and 1 new (ONO-1301) PGI2 analogs, on the expression of MIP-1α expression in human monocytes. Human primary monocytes from control subjects and THP-1 cell line were treated with PGI2 analogs, with or without lipopolysaccharide (LPS) stimulation. Supernatants were harvested to measure MIP-1α levels by enzyme-linked immunosorbent assay. To explore which receptors involved the effects of PGI2 analogs on the expression of MIP-1α expression, I prostanoid (IP) and E prostanoid, peroxisome proliferator-activated receptor (PPAR)-α, and PPAR-r receptor antagonists were used to pretreat THP-1 cells. Forskolin, a cyclic adenosine monophosphate (cAMP) activator, was also used to further confirm the cAMP involvement on the effect of PGI2 analogs in MIP-1α production.
  
  
  RESULTS
  Three PGI2 analogs could suppress LPS-induced MIP-1α production in THP-1 cells and human primary monocytes. ONO-1301 had a similar effect. CAY 10449, an IP receptor antagonist, could reverse the suppressive effects on MIP-1α production of iloprost. Forskolin, a cAMP activator, also suppressed MIP-1α production in THP-1 cells.
  
  
  CONCLUSIONS
  Prostaglandin I2 analogs suppressed LPS-induced MIP-1α production in human monocytes via the IP receptor and cAMP pathway. The PGI2 analog may be potential in the treatment for atherosclerosis.
authors.affiliation: From the *Division of Nephrology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung; †Department of Nursing, MeiHo University, Pingtung; ‡Division of Cardiac Surgery, Department of Surgery, §Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University; ∥Department of Pediatrics, E-DA Hospital, I-Shou University; ¶Department of Marine Biotechnology and Resources, National Sun Yat-sen University; **Graduate Institute of Medicine, College of Medicine, ††Department of Pediatrics, Kaohsiung Medical University Hospital, and Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University; ‡‡Department of Pediatrics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung; §§Department of Radiation Oncology, ∥∥Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University, and ¶¶Department of Pediatrics, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Tsai
authors.forename: Chong-Chao
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Hsuan-Fu
authors.initials: HF
authors.lastname: Kuo
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.forename: Chang-Hung
authors.initials: CH
authors.lastname: Kuo
authors.forename: Ming-Yii
authors.initials: MY
authors.lastname: Huang
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Tsai
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Lee
authors.forename: Chih-Hsing
authors.initials: CH
authors.lastname: Hung
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D054405:Chemokine CCL3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D016285:Iloprost / Q000031:analogs & derivatives / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D054405:Chemokine CCL3; C113936:PTGIR protein, human; D011725:Pyridines; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; C105488:ONO 1301; D011464:Epoprostenol; D000242:Cyclic AMP; D016285:Iloprost