Modulation of neutrophil motility by curcumin: Implications for inflammatory bowel disease

C. B. Larmonier, M. T. Midura-Kiela, R. Ramalingam, D. Laubitz, N. Janikashvili, N. Larmonier, F. K. Ghishan, P. R. Kiela

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

Background: Neutrophils (PMN) are the first cells recruited at the site of inflammation. They play a key role in the innate immune response by recognizing, ingesting, and eliminating pathogens and participate in the orientation of the adaptive immune responses. However, in inflammatory bowel disease (IBD) transepithelial neutrophil migration leads to an impaired epithelial barrier function, perpetuation of inflammation, and tissue destruction via oxidative and proteolytic damage. Curcumin (diferulolylmethane) displays a protective role in mouse models of IBD and in human ulcerative colitis, a phenomenon consistently accompanied by a reduced mucosal neutrophil infiltration. Methods: We investigated the effect of curcumin on mouse and human neutrophil polarization and motility in vitro and in vivo. Results: Curcumin attenuated lipopolysaccharide (LPS)-stimulated expression and secretion of macrophage inflammatory protein (MIP)-2, interleukin (IL)-1β, keratinocyte chemoattractant (KC), and MIP-1α in colonic epithelial cells (CECs) and in macrophages. Curcumin significantly inhibited PMN chemotaxis against MIP-2, KC, or against conditioned media from LPS-treated macrophages or CEC, a well as the IL-8-mediated chemotaxis of human neutrophils. At nontoxic concentrations, curcumin inhibited random neutrophil migration, suggesting a direct effect on neutrophil chemokinesis. Curcumin-mediated inhibition of PMN motility could be attributed to a downregulation of PI3K activity, AKT phosphorylation, and F-actin polymerization at the leading edge. The inhibitory effect of curcumin on neutrophil motility was further demonstrated in vivo in a model of aseptic peritonitis. Conclusions: Our results indicate that curcumin interferes with colonic inflammation partly through inhibition of the chemokine expression and through direct inhibition of neutrophil chemotaxis and chemokinesis. Inflamm Bowel Dis 2011

Original languageEnglish (US)
Pages (from-to)503-515
Number of pages13
JournalInflammatory bowel diseases
Volume17
Issue number2
DOIs
StatePublished - Feb 1 2011

Keywords

  • IL-8
  • KC
  • MIP-2
  • PMN
  • chemokinesis
  • chemotaxis
  • inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

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