title: Defensin DEFB103 bidirectionally regulates chemokine and cytokine responses to a pro-inflammatory stimulus.
abstract: Human β defensin DEFB103 acts as both a stimulant and an attenuator of chemokine and cytokine responses: a dichotomy that is not entirely understood. Our predicted results using an in silico simulation model of dendritic cells and our observed results in human myeloid dendritic cells, show that DEFB103 significantly (p < 0.05) enhanced 6 responses, attenuated 7 responses, and both enhanced/attenuated the CXCL1 and TNF responses to Porphyromonas gingivalis hemagglutinin B (HagB). In murine JAWSII dendritic cells, DEFB103 significantly attenuated, yet rarely enhanced, the Cxcl2, Il6, and Csf3 responses to HagB; and in C57/BL6 mice, DEFB103 significantly enhanced, yet rarely attenuated, the Cxcl1, Csf1, and Csf3 responses. Thus, DEFB103 influences pro-inflammatory activities with the concentration of DEFB103 and order of timing of DEFB103 exposure to dendritic cells, with respect to microbial antigen exposure to cells, being paramount in orchestrating the onset, magnitude, and composition of the chemokine and cytokine response.
authors: Dows Institute for Dental Research or Department of Periodontics, College of Dentistry, The University of Iowa, Iowa City, IA 52242, USA.
authors: Lauren E
authors: LE
authors: Harvey
authors: Karl G
authors: KG
authors: Kohlgraf
authors: Leslie A
authors: LA
authors: Mehalick
authors: Monica
authors: M
authors: Raina
authors: Erica N
authors: EN
authors: Recker
authors: Saumya
authors: S
authors: Radhakrishnan
authors: Samiksha Avinash
authors: SA
authors: Prasad
authors: Robinson
authors: R
authors: Vidva
authors: Ann
authors: A
authors: Progulske-Fox
authors: Joseph E
authors: JE
authors: Cavanaugh
authors: Shireen
authors: S
authors: Vali
authors: Kim A
authors: KA
authors: Brogden
mesh_terms: D018829:Adhesins, Bacterial / Q000633:toxicity; D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000633:toxicity; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016966:Porphyromonas gingivalis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023083:beta-Defensins / Q000494:pharmacology*
chemical_list: D018829:Adhesins, Bacterial; D054360:Chemokine CXCL1; D018925:Chemokines; D016207:Cytokines; C422950:DEFB103A protein, human; C098582:HagB protein, Porphyromonas gingivalis; D037102:Lectins; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D016173:Macrophage Colony-Stimulating Factor
references: PLoS One. 2010 Oct 22;5(10):e15389
references: 21042595
references: J Biol Chem. 2009 Oct 16;284(42):29180-92
references: 19640840
references: Adv Appl Bioinform Chem. 2010;3:97-110
references: 21918631
references: J Immunol. 2007 Jul 15;179(2):1245-53
references: 17617617
references: Eur J Immunol. 2011 Nov;41(11):3291-300
references: 21809339
references: Syst Synth Biol. 2010 Mar;4(1):25-33
references: 19856130
references: Cancer Invest. 2009 Jun;27(5):575-81
references: 19219676
references: Oral Microbiol Immunol. 2005 Jun;20(3):186-90
references: 15836521
references: J Pharmacol Exp Ther. 2011 Mar;336(3):672-81
references: 21159752
references: J Clin Periodontol. 2011 Mar;38 Suppl 11:126-41
references: 21323710
references: Int J Antimicrob Agents. 2012 Jul;40(1):75-9
references: 22578747
references: J Hematol Oncol. 2009 Feb 02;2:6
references: 19187543
references: Future Microbiol. 2010 Jan;5(1):115-25
references: 20020833
references: Periodontol 2000. 2009;51:152-80
references: 19878474
references: J Immunol. 2009 Aug 1;183(3):2122-32
references: 19596979
references: PLoS One. 2010 Jun 08;5(6):e10993
references: 20544025
references: J Clin Microbiol. 2006 May;44(5):1719-25
references: 16672398
references: Antimicrob Agents Chemother. 2008 May;52(5):1876-9
references: 18332171
references: J Invest Dermatol. 2007 Mar;127(3):594-604
references: 17068477
references: Cancer Chemother Pharmacol. 2010 Apr;65(5):903-11
references: 19685055
references: Curr Pharm Biotechnol. 2012 Aug;13(10):1882-97
references: 22250708
references: J Immunol. 2011 May 15;186(10):5772-83
references: 21498664
references: Nucleic Acids Res. 2011 Jan;39(Database issue):D514-9
references: 20929869
references: Nat Rev Immunol. 2012 Jun 25;12(7):503-16
references: 22728527
references: J Biol Chem. 2006 Jul 7;281(27):18787-92
references: 16648135
references: J Biol Chem. 2008 Feb 29;283(9):5414-9
references: 18167348
references: J Leukoc Biol. 2009 Oct;86(4):941-8
references: 19477909
references: Annu Rev Microbiol. 2003;57:57-76
references: 12730323
references: PLoS One. 2010 Jan 27;5(1):e8502
references: 20111699
references: Eur J Immunol. 2010 Apr;40(4):1073-8
references: 20104491
references: Immunol Cell Biol. 2008 Nov-Dec;86(8):643-9
references: 18711400
references: Neuroscience. 2011 Dec 29;199:303-17
references: 22056602
references: J Innate Immun. 2012;4(4):337-48
references: 22441423
references: Clin Cancer Res. 2011 Mar 15;17(6):1425-39
references: 21131551
references: Infect Immun. 2008 Dec;76(12):5714-20
references: 18852241
references: Antimicrob Agents Chemother. 2005 Sep;49(9):3883-8
references: 16127066
references: J Biol Chem. 2001 Feb 23;276(8):5707-13
references: 11085990
references: Antimicrob Agents Chemother. 2006 Apr;50(4):1433-41
references: 16569862
references: Injury. 2012 Feb;43(2):137-42
references: 21561617
references: J Biol Chem. 2008 Mar 14;283(11):6631-9
references: 18180295