PMID- 24157330 OWN - NLM STAT- MEDLINE DCOM- 20140902 LR - 20131206 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 17 IP - 4 DP - 2013 Dec TI - Curcumin inhibits agent-induced human neutrophil functions in vitro and lipopolysaccharide-induced neutrophilic infiltration in vivo. PG - 1101-7 LID - S1567-5769(13)00373-1 [pii] LID - 10.1016/j.intimp.2013.09.024 [doi] AB - Curcumin, extracted from the rhizome of Curcuma longa, is known to possess anti-inflammatory activities. Despite the fact that neutrophils are key player cells in inflammation, the role of curcumin on neutrophil cell biology is not well documented and, in particular, how curcumin can alter primed neutrophils is unknown. In addition, the effect of curcumin on agent-induced neutrophilic inflammation is not well documented. Here, we demonstrated that curcumin inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)- or lipopolysaccharide (LPS)-induced suppression of human neutrophil apoptosis. In addition, we found that curcumin reversed the ability of phorbol myristate acetate (PMA) to induce reactive oxygen species as assessed by flow cytometry using the CM-H2DCF-DA probe. Using an antibody array approach, curcumin was found to inhibit LPS-induced cytokine production, including MIP-1alpha, MIP-1beta, IL-6, IL-8 (CXCL-8) and GRO-alpha. The inhibitory effect of curcumin on IL-8 production was confirmed by ELISA. Using both an electrophoretic mobility shift assay and a TransFactor p50 NF-kappaB ELISA, we demonstrated that curcumin inhibited LPS-induced NF-kappaB activation. In vivo, using the murine air pouch model of acute inflammation, we demonstrated that intraperitoneal administration of curcumin inhibited LPS-induced neutrophilic infiltration in vivo. As assessed by a murine antibody array approach, curcumin was found to decrease the local production of several cytokines/chemokines induced by LPS, including, but not limit to, MIP-1alpha and MIP-1beta. We conclude that curcumin possesses potent modulatory activities on primed or agent-induced human neutrophils in vitro and that it possesses important anti-inflammatory activities in vivo by inhibiting LPS-induced neutrophilic inflammation. CI - (c) 2013. FAU - Antoine, Francis AU - Antoine F AD - Laboratoire de recherche en inflammation et physiologie des granulocytes, Universite du Quebec, INRS-Institut-Armand-Frappier, Laval, Quebec Canada. FAU - Simard, Jean-Christophe AU - Simard JC FAU - Girard, Denis AU - Girard D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131021 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (Interleukin-8) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 0 (Reactive Oxygen Species) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Apoptosis/drug effects MH - Cells, Cultured MH - Curcumin/*pharmacology MH - Cytokines/metabolism MH - Female MH - Humans MH - Inflammation/metabolism MH - Interleukin-8/metabolism MH - Lipopolysaccharides MH - Mice MH - NF-kappa B/metabolism MH - Neutrophils/*drug effects/metabolism MH - Reactive Oxygen Species/metabolism OTO - NOTNLM OT - Curcumin OT - Immunomodulation OT - Inflammation OT - Neutrophils EDAT- 2013/10/26 06:00 MHDA- 2014/09/03 06:00 CRDT- 2013/10/26 06:00 PHST- 2013/08/14 00:00 [received] PHST- 2013/09/18 00:00 [revised] PHST- 2013/09/30 00:00 [accepted] PHST- 2013/10/26 06:00 [entrez] PHST- 2013/10/26 06:00 [pubmed] PHST- 2014/09/03 06:00 [medline] AID - S1567-5769(13)00373-1 [pii] AID - 10.1016/j.intimp.2013.09.024 [doi] PST - ppublish SO - Int Immunopharmacol. 2013 Dec;17(4):1101-7. doi: 10.1016/j.intimp.2013.09.024. Epub 2013 Oct 21.