Butyrate enhancement of inteleukin-1β production via activation of oxidative stress pathways in lipopolysaccharide-stimulated THP-1 cells

Abstract

In inflammatory bowel diseases, interleukin-1β production is accelerated. Butyrate, a short chain fatty acid, plays an important role in inflammatory bowel diseases. We investigated the effect of butyrate on interleukin-1β production in macrophage and elucidated its underlying mechanism. We stimulated THP-1 cells, a human premonocytic cell line, by lipopolysaccharide alone and by butyrate with lipopolysaccharide. Butyrate with lipopolysaccharide increased interleukin-1β production more than lipopolysaccharide alone. Butyrate with lipopolysaccharide increased caspase-1 activity more than lipopolysaccharide alone. As for the phosphorylation pathway, PD98059 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor) decreased caspase-1 activity and interleukin-1β production to approximately 50% of the controls. Pertussis toxin (G protein-coupled signal transduction pathway inhibitor) also reduced interleukin-1β production to approximately 50%. Butyrate with lipopolysaccharide increased reactive oxygen species levels more than lipopolysaccharide alone. The addition of N-acetyl L-cysteine reduced reactive oxygen species levels to a level similar to that of lipopolysaccharide alone. Butyrate with lipopolysaccharide increased nitric oxide production more than lipopolysaccharide alone, and the addition of N-acetyl L-cysteine reduced the elevated amount of nitric oxide. In conclusions, butyrate enhances interleukin-1β production by activating caspase-1, via reactive oxygen species, the phosphorylation of MAPK, and G protein mediated pathways in lipopolysaccharide stimulated THP-1 cells.

High Fiber Diet Decreases the Level of Interleukin 1

“…It was in line with the previous study which states that a high fiber diet can reduce inflammatory responses characterized by lower IL-1β [24]. It was suspected to be due to SCFA contents, especially butyrate, one of the results of fermentation of food fiber, suppressing cytokines which stimulate the production of inflammatory mediators such as IL-1β [25]. The main mechanism which could explain the effect was reduced HDAC activity [26].…”

“…Short chain fatty acids worked with cytokines in leukocytes and endothelial cells through two mechanisms, i.e. GPR activation HDAC inhibition [25]. Short chain fatty acids regulated cytokine production, including IL-1β [13].…”

Butyrate Attenuates Inflammation and Lipolysis Generated by the Interaction of Adipocytes and Macrophages

“…Conversely, we also acknowledge the possibility that co-culture induces the initial production of inflammatory mediators, followed by lipolysis 6) . On the other hand, we previously demonstrated that butyrate enhances IL-1β production via the activation of oxidative stress pathways in lipopolysaccharidestimulated THP-1 cells 38) . Although the culture condition in the previous study is different from the present study, butyrate appears to have acceleratory or inhibitory effects on the macrophage-mediated inflammatory response.…”

Supplementation of sodium butyrate protects mice from the development of non-alcoholic steatohepatitis (NASH)

“…However, no signs of inflammation were seen in livers of these control mice. In in vitro studies of Ohira et al ( 28 ) , it was shown that an incubation of macrophages with butyrate especially in the presence of endotoxin is associated with an increased expression of IL-1β . Furthermore, Mattace et al ( 6 ) also reported a non-significant approximately 2-fold increase in IL-1β expression and cyclo-oxygenase-2 (COX-2) protein levels in livers of control rats fed a diet enriched with butyrate (20 mg/kg body weight).…”