Journal
BIOENGINEERED
Volume 12, Issue 1, Pages 151-161Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/21655979.2020.1859259
Keywords
Fenretinide; ulcerative colitis; macrophage polarization; PPAR-γ RAW264; 7 cells
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The study demonstrated that 4-HPR may be a potent anti-UC agent that works by regulating macrophage polarization via PPAR gamma.
Fenretinide (4-HPR), a synthetic retinoid, has attracted attention for its anti-inflammation activity. However, few studies have evaluated the effects of 4-HPR on ulcerative colitis (UC). The present study was performed to investigate the therapeutic effects of 4-HPR on UC, and to explore the mechanisms mainly focused on macrophage polarization involved in this progress. Intraperitoneally administered 4-HPR particularly at dose of 100 mg/kg obviously alleviated UC symptoms and restrained the mRNA expression of colonic IL-1 beta, IL-6, and TNF-alpha in dextran sulfate sodium (DSS)-induced mice. Further analysis showed that 4-HPR decreased the mRNA expression of M1 macrophage markers IL-12 and iNOS, while increased M2 macrophage markers Ym1, Arg1 and MRC1 in colonic tissue of mice received DSS. Consistently, an in vitro study revealed that 4-HPR decreased inflammatory response and M1 polarization, while enhanced M2 polarization in LPS-induced RAW264.7 cells. Interestingly, 4-HPR remarkably activated PPAR-gamma which was an important regulator of macrophage polarization both in colonic tissue of UC mice and in LPS-induced RAW264.7 cells. Furthermore, these effects of 4-HPR in vivo and in vitro including anti-inflammation and modulation of macrophage polarization were partially abolished by treatment with PPAR-gamma antagonist GW9662, indicating that 4-HPR activated PPAR-gamma to exert its activities. Taken together, this study demonstrated that 4-HPR might be a potent anti-UC agent that works by regulating macrophage polarization via PPAR gamma.
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