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Mediators of Inflammation
Volume 2018 (2018), Article ID 2868702, 13 pages
https://doi.org/10.1155/2018/2868702
Research Article

Bisdemethoxycurcumin and Its Cyclized Pyrazole Analogue Differentially Disrupt Lipopolysaccharide Signalling in Human Monocyte-Derived Macrophages

1Venetian Institute of Molecular Medicine, Padua, Italy
2Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy
3Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna, Italy
4Department of Medicine, University of Padua, Padua, Italy

Correspondence should be addressed to Chiara Bolego; ti.dpinu@ogelob.araihc

Received 28 July 2017; Revised 31 October 2017; Accepted 29 November 2017; Published 8 February 2018

Academic Editor: Vinod K. Mishra

Copyright © 2018 Serena Tedesco et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Several studies suggest that curcumin and related compounds possess antioxidant and anti-inflammatory properties including modulation of lipopolysaccharide- (LPS-) mediated signalling in macrophage cell models. We here investigated the effects of curcumin and the two structurally unrelated analogues GG6 and GG9 in primary human blood-derived macrophages as well as the signalling pathways involved. Macrophages differentiated from peripheral blood monocytes for 7 days were activated with LPS or selective Toll-like receptor agonists for 24 h. The effects of test compounds on cytokine production and immunophenotypes evaluated as CD80+/CCR2+ and CD206+/CD163+ subsets were examined by ELISA and flow cytometry. Signalling pathways were probed by Western blot. Curcumin (2.5–10 μM) failed to suppress LPS-induced inflammatory responses. While GG6 reduced LPS-induced IκB-α degradation and showed a trend towards reduced interleukin-1β release, GG9 prevented the increase in proinflammatory CD80+ macrophage subset, downregulation of the anti-inflammatory CD206+/CD163+ subset, increase in p38 phosphorylation, and increase in cell-bound and secreted interleukin-1β stimulated by LPS, at least in part through signalling pathways not involving Toll-like receptor 4 and nuclear factor-κB. Thus, the curcumin analogue GG9 attenuated the LPS-induced inflammatory response in human blood-derived macrophages and may therefore represent an attractive chemical template for macrophage pharmacological targeting.