Abstract
BACKGROUND: Sepsis, an uncontrolled host response to infection, may be life-threatening organ injury. Neutrophils play a critical role in regulation of host immune response to infection. Curcumin, known as a spice and food coloring agent, possesses anti-inflammatory properties. In this study, we investigated the effects of curcumin on lipopolysaccharide (LPS)-induced neutrophil activation with its signaling pathways. METHODS: Isolated human neutrophils were incubated without or with LPS and curcumin, and the expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-8 were assessed by enzyme-linked immunosorbent assays. The expression of mitogen-activated protein kinases such as p38, extracellularsignal-regulated kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK) were evaluated by Western blot analysis. Neutrophil apoptosis was also measured by fluorescence-activated cell sorting (annexin V/propidium iodide) in LPS-stimulated neutrophils under treatment with curcumin. RESULTS: Curcumin attenuated expression of TNF-α, IL-6, and IL-8 and the phosphorylation levels of p38 and JNK, but not ERK1/2, in LPS-stimulated neutrophils. Additionally, curcumin restored the delayed neutrophil apoptosis by LPS-stimulated neutrophils(19.7 ± 3.2 to 38.2 ± 0.5%, P < 0.05). CONCLUSIONS: Our results reveal the underlying mechanism of how curcumin attenuate neutrophil activation and suggest potential clinic applications of curcumin supplementation for patients with severe sepsis and septic shock. Additional clinical studies are required to confirm these in vitro findings.