Spirulina platensis inhibits lipopolysaccharide‐induced inflammation through the repression of histone deacetylases in RAW 264.7 macrophages

Abstract

We observed a potent anti‐inflammatory effect of Spirulina platensis (SP), an edible blue‐green alga, in vitro and ex vivo. To gain a mechanistic insight into the anti‐inflammatory effect of SP organic extract (SPE), we examined the effect of SPE on the expression of histone deacetylases (HDAC) 1 to 11 in lipopolysaccharide (LPS)‐activated RAW 264.7 macrophages. When macrophages were treated with LPS alone (100 ng/ml), SPE alone (100 μg/ml), or SPE+LPS, mRNA and protein levels of most HDAC isoforms were significantly decreased. However, one striking difference was that HDAC1 and HDAC3 protein levels were markedly decreased by SPE but LPS had a minimal effect. The potent repression of HDAC by SPE was evidenced by a marked increase in histone 3 acetylation to a similar extent to that of 25 nM trichostatin A (TSA), a pan HDAC inhibitor. When LPSactivated macrophages were treated with TSA (25 nM), proinflammatory cytokine expression including tumor necrosis factor α and interleukin 1β was significantly decreased but the reduction was less than that of SPE (50 or 100 μg/ml). The repressive effect of SPE on HDAC is likely cell type‐specific because this effect was also observed in 3T3‐L1 preadipocytes but not in HepG2 and Caco‐2 cells. In conclusion, SPE exerts its anti‐inflammatory effect at least in part by a HDAC‐dependent mechanism via the repression of HDAC1 and HDAC3 in macrophages.Grant Funding Source: NIH R21AT005152