A Prostacyclin Analog, Cicaprost, Exhibits Potent Anti-Inflammatory Activity in Human Primary Immune Cells and a Uveitis Model.

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A Prostacyclin Analog, Cicaprost, Exhibits Potent Anti-Inflammatory Activity in Human Primary Immune Cells and a Uveitis Model.

J Ocul Pharmacol Ther. 2017 Apr;33(3):186-192

Authors: Wang JW, Vu C, Poloso NJ

Abstract
PURPOSE: To investigate the therapeutic potential of a prostacyclin (IP) receptor agonist for ocular inflammation and the effect on immune cells.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.

PMID: 28072560 [PubMed - indexed for MEDLINE]

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