Pentadecyl®, an odd-chain-rich triglyceride mixture derived from Aurantiochytrium oil, attenuates lipopolysaccharide-induced inflammatory cytokine production in BV-2 microglial cells

Background and aim: Microglia are the primary immune cells of the central nervous system that play pivotal roles in health and disease. Abnormally activated microglia secrete proinflammatory factors and play essential roles in neurodegenerative disease progression. This study investigated the potential effects of Pentadecyl, rich in odd-numbered fatty acids, such as pentadecanoic acid, isolated from Aurantiochytrium limacinum, on the lipopolysaccharide (LPS)-induced immune response of BV-2 microglial cells. Experimental procedure: Cell viability was detected using MTT and LIVE/DEAD assays. mRNA and protein levels of inflammatory cytokines and signaling factors were assessed using real-time PCR and western blotting, respectively. Results and conclusion: Pentadecyl did not affect MTT-reducing activity or the number of dead cells stained with ethidium homodimer-1. Pentadecyl selectively mitigated the LPS-induced overproduction of pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, at the transcriptional and protein levels, whereas tumor necrosis factor-alpha (TNF-α) expression remained unchanged. Western blot analysis showed that Pentadecyl downregulated the LPS-induced increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) but did not affect the phosphorylation of p65, a component of nuclear factor-kappa B, or p38 and c-Jun N-terminal kinase, both of which are mitogen-activated protein kinases. Similar to Pentadecyl, Stattic, a representative STAT3 inhibitor, preferentially suppressed the LPS-induced upregulation of IL-6 and IL-1β mRNA expression, whereas its inhibitory effect on TNF-α expression was relatively modest. These results indicate that Pentadecyl suppresses LPS-induced pro-inflammatory cytokine production without affecting cell survival by regulating the STAT3 signaling pathway in BV-2 cells.