Abstract
Purpose: To investigate the inhibitory effects of a chalcone derivative on lipopolysaccharide (LPS)- induced interleukin (IL)-6 and IL-8 secretions and on LPS-induced mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB) activation in human U937 macrophage-like cell line.
 Methods: The effects of chalcone derivative on LPS-induced secretion of IL-6 and IL-8 in endothelial cells were determined by enzyme-linked immunosorbent assay while the effects of chalcone on the activation of MAPK and NF-kB pathway were determined by Western blotting.
 Results: The results showed that 3-(5-methyl-furan-2-yl)-naphthalen-1-yl-propenone (compound 1) significantly inhibited the secretion of LPS-induced IL-6 and IL-8 in U937 macrophages. This compound also demonstrated significant suppression of c-Jun N-terminal kinases (JNK) and extracellular signalregulated kinases (ERK) phosphorylation. However, the compound did not reverse the degradation of inhibitor kappa B alpha (IκBα) and did not inhibit the phosphorylation of NF-κB subunit and P-38 MAPK.
 Conclusion: Compound 1 inhibits the secretion of cytokines via the inhibition of ERK and JNK pathways. These results suggest that chalcone derivative could act as an antiinflammatory agent by altering cytokine secretion and inflammatory pathways.
Highlights
Inflammation is a crucial component of the complex biological response of body tissues against detrimental stimuli [1]
Concentrations of compound 1 used in this study were selected based on the concentrations that did not cause more than 10% U937 macrophage cell death, as reported in our previous work [10]
A study conducted by Clahsen and Schaper revealed that the role of IL-6 as the pro-inflammatory cytokine by promoting monocytic cell migration through a number of processes such as integrin activation, cell attachment, polymerisation of actin, chemotaxis and fibronectin-dependent migration [16]
Summary
Inflammation is a crucial component of the complex biological response of body tissues against detrimental stimuli [1]. Chronic and excessive inflammation will cause several diseases such as rheumatoid arthritis and atherosclerosis. Activated macrophages serve an important role in establishing inflammation by inducing the secretion of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-8 (IL-8). IL-6 is a cytokine which induces neutrophil maturation as well as cytotoxic T-lymphocyte and natural killer cell differentiation [2]. Whilst IL-8 promotes chemotaxis and directs migration of leucocytes to the target site for immune responses [3]. Chalcones (1,3-diaryl-2-propen-ones) are α, β unsaturated ketones with two aromatic rings, EXPERIMENTAL
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