Butyrate modulation of inflammatory responses to lipopolysaccharide in porcine monocytes

Abstract

Abstract Butyrate is a short-chain fatty acid produced through microbial fermentation of dietary fibers in the lower intestinal tract. Butyrate production is associated with enhanced mucosal immunity, increased barrier integrity, and modulation of immune cells. Butyrate driven immunomodulation occurs through a variety of mechanisms, including histone deacetylase (HDAC) inhibitor activity and inhibition of NF-kB signaling. Butyrate impacts lipopolysaccharide (LPS)-induced cytokine production and gene expression by porcine monocytes in a dose-dependent manner. To investigate the mechanisms driving butyrate modulation of porcine monocyte responses to LPS, peripheral monocytes were cultured with LPS +/− butyrate. After incubation, cells were processed for collection of cytoplasmic and nuclear fractions. HDAC activity in nuclear fractions and NF-kB signaling state (IkBa, p-IkBa, p65, p-p65) in cytoplasmic fractions was assessed. Butyrate did not inhibit HDAC activity after 1 hour (h) but at 24 h, butyrate exposure resulted in inhibition of HDAC activity regardless of LPS exposure, in a dose-dependent manner. Neither the low nor high concentration of butyrate altered IkBa, p-IkBa, p65, or p-p65 status, though p-IkBa and p-p65 status was dependent on LPS exposure. Overall, the impact of butyrate on HDAC activity was time and dose-dependent, and butyrate had little to no effect on NF-kB signaling induced by LPS exposure. Continued investigation is warranted to understand the potential mechanisms driving butyrate modulation of monocyte responses to LPS to enhance abilities to modulate immune status. USDA-ARS CRIS 005