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Opioid Compounds Inhibit Hepatic Stellate Cell Activation and Collagen Expression: A Possible Mechanism for Attenuation of Liver Fibrosis
Author(s) -
Day Stephani A,
Clemens Mark G,
Wu Edwin,
Schrum Laura W
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1190.11
Subject(s) - hepatic stellate cell , chemistry , receptor , microbiology and biotechnology , pharmacology , medicine , biochemistry , biology
Hepatic fibrosis is characterized by activated hepatic stellate cells (HSCs) and increased type I collagen deposition. JKB‐122, an opioid compound, protects against liver fibrosis. JKB‐121, an analog of JKB‐122, is predicted to have a similar efficacy. Both JKB‐122 and JKB‐121 are known to bind to opiate receptors and to modulate inflammatory cytokine activities. JKB‐119, an opioid‐like compound, has anti‐inflammatory activity without any significant binding affinity to opiate receptors. To delineate which activity is attributed to the anti‐fibrotic activity, we determined the effects JKB‐119 and JKB‐121 had on HSC activation and collagen expression. HSCs were culture‐activated and treated with each drug, and RT‐PCR and Western blots were performed to determine collagen and smooth muscle α–actin (SMA) expression. HSCs treated with JKB‐119 or JKB‐121 showed a decrease in collagen and SMA mRNA expression. Similarly, SMA protein concentrations were reduced. These data suggest that the anti‐inflammatory properties of these drugs may act directly on HSC activation and collagen production abrogating liver fibrosis without modulation of opiate receptors. Understanding how HSCs respond to each of these drugs and what role opiate receptor signaling plays in these cells can lead to the development of novel therapeutics for liver fibrosis. Supported by SRL of North Carolina Biotechnology Center.