title: A Prostacyclin Analog, Cicaprost, Exhibits Potent Anti-Inflammatory Activity in Human Primary Immune Cells and a Uveitis Model.
abstract: To investigate the therapeutic potential of a prostacyclin (IP) receptor agonist for ocular inflammation and the effect on immune cells.
  
  
  
  The anti-inflammatory activities of cicaprost were determined in primary human monocyte-derived macrophages and human monocyte-derived dendritic cells (MoDC), as well as a lipopolysaccharides (LPS)-induced rat uveitis model. Multiple cytokine release was measured by utilizing Luminex Technology. Prostacyclin (IP) Receptor expression was detected by reverse transcription-polymerase chain receptor. Leukocyte infiltration and protein exudation in the rat uveitis model were measured using a hemocytometer and protein concentration by a NanoDrop instrument.
  
  
  
  Cicapost, an IP receptor agonist, potently inhibits proinflammatory chemokines/cytokine production not only from LPS- or TNFα (tumor necrosis factor-alpha)-induced primary human monocyte-derived macrophages, but also from LPS-stimulated MoDC. While constitutively expressed in macrophages, the IP receptor was inducible by LPS stimulation in MoDCs. In a LPS-induced rat uveitis model, cicaprost efficaciously prevents ocular inflammatory cell and protein leakage, as well as inflammatory cytokine release.
  
  
  
  The IP receptor agonist cicaprost is a potent anti-inflammatory agent, implicating that the tightly controlled PGI2/IP signaling pathway is important in regulating inflammation. This response could be harnessed in ocular inflammatory disease where steroids are currently the standard of care.
authors.affiliation: Department of Biological Sciences, Allergan , Irvine, California.
authors.forename: Jenny W
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, Allergan , Irvine, California.
authors.forename: Chau
authors.initials: C
authors.lastname: Vu
authors.affiliation: Department of Biological Sciences, Allergan , Irvine, California.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Poloso
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011917:Rats, Inbred Lew; D044006:Receptors, Epoprostenol / Q000819:agonists / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D008070:Lipopolysaccharides; C113936:PTGIR protein, human; D044006:Receptors, Epoprostenol; D014409:Tumor Necrosis Factor-alpha; D011464:Epoprostenol; C043867:cicaprost
keywords: dendritic cells; inflammation; macrophages; ocular; prostacyclin