title: Topical curcumin can inhibit deleterious effects of upper respiratory tract bacteria on human oropharyngeal cells in vitro: potential role for patients with cancer therapy induced mucositis?
abstract: OBJECTIVE
  Curcumin exerts its anti-inflammatory activity via inhibition of nuclear factor κB. Oropharyngeal epithelia and residing bacteria closely interact in inflammation and infection. This in vitro model investigated the effects of curcumin on bacterial survival, adherence to, and invasion of upper respiratory tract epithelia, and studied its anti-inflammatory effect. We aimed to establish a model, which could offer insights into the host-pathogen interaction in cancer therapy induced mucositis.
  
  
  METHODS
  Moraxella catarrhalis (Mcat) and the oropharyngeal epithelial cell line Detroit 562 were used. Time-kill curves assessed the inhibition of bacterial growth and adherence assays and gentamicin protection assays determined the effect of curcumin-preincubated cells on bacterial adherence and invasion. Curcumin-mediated inhibition of pro-inflammatory activation by Mcat was determined via interleukin-8 concentrations in the supernatants. The synergistic role of secretory IgA (sIgA) on adherence was investigated.
  
  
  RESULTS
  Curcumin was bactericidal at concentrations >50 µM. Preincubation of Detroit cells for 60 min demonstrated that concentrations >100 µM inhibited bacterial adherence. Together with sIgA, curcumin inhibited adherence at concentrations ≥50 µM. Both 100 and 200 µM curcumin significantly inhibited Mcat cell invasion. Finally, curcumin inhibited Mcat-induced pro-inflammatory activation by strongly suppressing IL-8 release. At a concentration of 200 µM, 10 min of curcumin exposure inhibited IL-8 release significantly, and complete suppression required a pre-exposure time of ≥45 min.
  
  
  CONCLUSIONS
  Curcumin, in clinically relevant concentrations for topical use, displayed strong antibacterial effect against a facultative upper respiratory tract pathogen by inhibiting bacterial growth, adherence, invasion, and pro-inflammatory activation of upper respiratory tract epithelial cells in vitro.
authors.affiliation: Department of Pediatrics, University of Bern, Inselspital, 3010, Bern, Switzerland.
authors.forename: Sonja
authors.initials: S
authors.lastname: Lüer
authors.forename: Rolf
authors.initials: R
authors.lastname: Troller
authors.forename: Marion
authors.initials: M
authors.lastname: Jetter
authors.forename: Violeta
authors.initials: V
authors.lastname: Spaniol
authors.forename: Christoph
authors.initials: C
authors.lastname: Aebi
mesh_terms: D000287:Administration, Topical; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000382:microbiology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000008:administration & dosage*; D016209:Interleukin-8 / Q000378:metabolism; D001936:Moraxella catarrhalis / Q000187:drug effects*; D045828:Moraxellaceae Infections / Q000188:drug therapy / Q000382:microbiology; D009960:Oropharynx / Q000166:cytology / Q000382:microbiology; D013280:Stomatitis / Q000188:drug therapy / Q000209:etiology / Q000382:microbiology; D013997:Time Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007071:Immunoglobulin A, Secretory; D016209:Interleukin-8; D003474:Curcumin
references.citation: J Oncol. 2008;2008:907892
references.pmid: 19259334
references.citation: Clin Infect Dis. 2004 Jan 15;38(2):234-42
references.pmid: 14699456
references.citation: Am J Med. 2000 Sep;109(4):288-95
references.pmid: 10996579
references.citation: J Biol Chem. 2002 Mar 1;277(9):7438-46
references.pmid: 11751883
references.citation: J Infect Dis. 1988 Oct;158(4):761-5
references.pmid: 3139777
references.citation: EMBO J. 1998 Sep 1;17(17):5170-81
references.pmid: 9724653
references.citation: Pediatrics. 2006 May;117(5):1823-9
references.pmid: 16651345
references.citation: J Antimicrob Chemother. 2009 May;63 Suppl 1:i36-40
references.pmid: 19372181
references.citation: Int J Radiat Biol. 2004 Feb;80(2):177-82
references.pmid: 15164799
references.citation: Curr Opin Infect Dis. 2009 Jun;22(3):279-85
references.pmid: 19405217
references.citation: J Infect Dis. 2007 Oct 1;196(7):1080-7
references.pmid: 17763332
references.citation: J Infect Dis. 2009 Nov 15;200(10):1593-601
references.pmid: 19835476
references.citation: Int J Oral Surg. 1985 Oct;14(5):416-27
references.pmid: 3932235
references.citation: Eur J Clin Microbiol Infect Dis. 1996 Apr;15(4):291-6
references.pmid: 8781879
references.citation: J Biol Chem. 1995 Oct 20;270(42):24995-5000
references.pmid: 7559628
references.citation: J Infect Dis. 1993 Nov;168(5):1194-201
references.pmid: 8228353
references.citation: J Agric Food Chem. 2009 May 13;57(9):3765-70
references.pmid: 19317462
references.citation: Oral Oncol. 1998 Jan;34(1):39-43
references.pmid: 9659518
references.citation: Clin Infect Dis. 2009 Jul 1;49(1):124-31
references.pmid: 19480579
references.citation: Microbes Infect. 2008 Jan;10(1):3-11
references.pmid: 18069032
references.citation: Cancer. 2003 Oct 1;98(7):1531-9
references.pmid: 14508842
references.citation: Biochem J. 2008 Feb 15;410(1):147-55
references.pmid: 17953519
references.citation: Cancer Treat Rev. 2007 Aug;33(5):448-60
references.pmid: 17507164
references.citation: FEMS Immunol Med Microbiol. 2006 Mar;46(2):198-208
references.pmid: 16487301
references.citation: Cell Microbiol. 2007 Dec;9(12):2968-83
references.pmid: 17764466
references.citation: Biol Chem. 2005 May;386(5):481-90
references.pmid: 15927892
references.citation: Infect Immun. 1997 Nov;65(11):4367-77
references.pmid: 9353007
references.citation: Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L818-26
references.pmid: 16399788
references.citation: J Clin Immunol. 2007 Jan;27(1):19-35
references.pmid: 17211725
references.citation: Lancet. 2004 Feb 7;363(9407):465-73
references.pmid: 14962529
references.citation: Leukemia. 2004 Feb;18(2):276-84
references.pmid: 14671640
references.citation: J Infect Dis. 1994 Jun;169(6):1312-7
references.pmid: 8195609
references.citation: Eur Respir J. 2008 Apr;31(4):725-35
references.pmid: 18184679
references.citation: Infect Immun. 1998 Jul;66(7):3113-9
references.pmid: 9632574
references.citation: Cell Microbiol. 2007 Mar;9(3):694-707
references.pmid: 17054439