3,3'-Diindolylmethane stimulates murine immune function in vitro and in vivo.
3,3'-Diindolylmethane (DIM), a major condensation product of indole-3-carbinol, exhibits chemopreventive properties in animal models of cancer. Recent studies have shown that DIM stimulates interferon-gamma (IFN-gamma) production and potentiates the IFN-gamma signaling pathway in human breast cancer cells via a mechanism that includes increased expression of the IFN-gamma receptor. The goal of this study was to test the hypothesis that DIM modulates the murine immune function. Specifically, the effects of DIM were evaluated in a panel of murine immune function tests that included splenocyte proliferation, reactive oxygen species (ROS) generation, cytokine production and resistance to viral infection. DIM was found to induce proliferation of splenocytes as well as augment mitogen- and interleukin (IL)-2-induced splenocyte proliferation. DIM also stimulated the production of ROS by murine peritoneal macrophage cultures. Oral administration of DIM, but not intraperitoneal injection, induced elevation of serum cytokines in mice, including IL-6, granulocyte colony-stimulating factor (G-CSF), IL-12 and IFN-gamma. Finally, in a model of enteric virus infection, oral DIM administration to mice enhanced both clearance of reovirus from the GI tract and the subsequent mucosal IgA response. Thus, DIM is a potent stimulator of immune function. This property might contribute to the cancer inhibitory effects of this indole.
Xue
Ling
L
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, USA.
Pestka
James J
JJ
Li
Maoxiang
M
Firestone
Gary L
GL
Bjeldanes
Leonard F
LF
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007109:Immunity / Q000187:drug effects*; D007070:Immunoglobulin A / Q000187:drug effects / Q000276:immunology; D007211:Indoles / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D030102:Orthoreovirus, Mammalian / Q000187:drug effects / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012088:Reoviridae Infections / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000914:Antibodies, Viral; D016588:Anticarcinogenic Agents; D016207:Cytokines; D007070:Immunoglobulin A; D007211:Indoles; D017382:Reactive Oxygen Species; C016392:3,3'-diindolylmethane
Biochem Biophys Res Commun. 1988 Nov 30;157(1):87-94
3196352
J Exp Med. 1991 Mar 1;173(3):647-58
1900079
J Virol. 2001 Nov;75(22):10870-9
11602727
J Virol. 1982 Oct;44(1):393-400
6292500
Blood. 2001 Jan 1;97(1):192-7
11133760
Chem Res Toxicol. 1992 Mar-Apr;5(2):188-93
1643248
J Virol. 1988 Dec;62(12):4594-604
2460637
J Immunol. 2001 Mar 1;166(5):3114-21
11207263
Obstet Gynecol Clin North Am. 1996 Sep;23(3):699-706
8869953
J Leukoc Biol. 1994 Feb;55(2):280-8
7905508
Carcinogenesis. 2002 Aug;23(8):1297-305
12151347
J Virol. 1996 Sep;70(9):5968-74
8709219
Cancer Immunol Immunother. 1999 May-Jun;48(2-3):63-70
10414459
J Mol Cell Immunol. 1989;4(4):203-11; discussion 211-2
2610854
J Nutr. 2003 Jul;133(7 Suppl):2448S-2455S
12840223
J Toxicol Environ Health A. 2000 Feb 25;59(4):271-9
10706034
Antivir Ther. 2002 Mar;7(1):1-9
12008782
Arch Dermatol. 1998 Jan;134(1):25-30
9449906
Curr Opin Otolaryngol Head Neck Surg. 2003 Dec;11(6):433-41
14631175
Immunol Invest. 2004;33(4):407-21
15624699
Oncogene. 2005 Mar 31;24(14):2343-53
15735741
Immunity. 1994 Sep;1(6):447-56
7895156
Cell Immunol. 1991 Nov;138(1):11-23
1913833
Curr Protoc Immunol. 2004 May;Chapter 3:Unit 3.12
18432927
J Exp Med. 1988 Feb 1;167(2):332-44
3258006
Arch Immunol Ther Exp (Warsz). 2006 Jan-Feb;54(1):15-24
16642253
Curr Protoc Immunol. 2001 May;Chapter 7:7.10.1-7.10.10
18432824
J Virol. 2004 Apr;78(7):3352-60
15016857
Cytokine Growth Factor Rev. 2002 Dec;13(6):441-54
12401479
J Immunol. 1994 Aug 15;153(4):1697-706
7913943
J Exp Med. 1989 Jun 1;169(6):2133-48
2786548
J Mol Cell Cardiol. 2004 May;36(5):707-10
15135666
Toxicol Sci. 2005 Sep;87(1):134-45
15958657
Trends Microbiol. 2001 Nov;9(11):560-4
11825717
Biochem Pharmacol. 2000 Jul 15;60(2):167-77
10825461
Anticancer Res. 1999 May-Jun;19(3A):1673-80
10470100
Curr Opin Microbiol. 2001 Jun;4(3):251-9
11378475
Cancer. 2004 Oct 15;101(8):1767-75
15386335
Immunol Today. 1997 Oct;18(10):493-7
9357142
Annu Rev Immunol. 1998;16:495-521
9597139
Carcinogenesis. 2005 Apr;26(4):771-8
15661811
Annu Rev Immunol. 1984;2:283-318
6100475
Curr Top Microbiol Immunol. 1999;238:57-78
10087650
J Biol Chem. 2001 Jun 22;276(25):22332-40
11297539
J Exp Med. 1987 Mar 1;165(3):830-47
2950199
Cell Immunol. 1998 Aug 25;188(1):55-63
9743558
Cancer Res. 2000 Jan 15;60(2):359-64
10667588
Med Hypotheses. 2001 May;56(5):558-66
11388769
Mol Pharmacol. 2006 Feb;69(2):430-9
16267208
J Immunol. 2005 Jun 15;174(12):7610-7
15944261
J Virol. 1997 Aug;71(8):5782-9
9223466
Am J Otolaryngol. 1997 Jul-Aug;18(4):283-5
9242883
J Immunol. 1984 Apr;132(4):1980-6
6321594
Carcinogenesis. 1998 Sep;19(9):1631-9
9771935
J Toxicol Environ Health A. 2001 Apr 6;62(7):561-73
11289704
Cancer Res. 2006 May 1;66(9):4880-7
16651444
Otolaryngol Head Neck Surg. 1998 Jun;118(6):810-5
9627242
Antimicrob Agents Chemother. 1998 Apr;42(4):789-94
9559784
Curr Opin Immunol. 2001 Aug;13(4):458-64
11498302
J Am Acad Dermatol. 1998 Feb;38(2 Pt 1):230-9
9486679
Biochem Pharmacol. 2002 Mar 15;63(6):1085-97
11931841
Trends Immunol. 2001 Mar;22(3):113-5
11286714
J Immunol. 2005 Dec 1;175(11):7085-91
16301609
Toxicol Sci. 1998 Apr;42(2):99-108
9579022
Trends Immunol. 2002 Apr;23(4):201-8
11923115
J Virol. 1990 Mar;64(3):1256-63
2154608
Eur J Immunol. 1993 Jun;23(6):1333-9
8388798
Cancer Res. 1978 May;38(5):1410-3
416908
Toxicol Appl Pharmacol. 2006 Aug 1;214(3):318-25
16504231
Reprod Fertil Dev. 1994;6(3):389-92
7831487
Cytokine Growth Factor Rev. 2004 Oct;15(5):367-77
15450252
J Immunol. 1988 Jan 15;140(2):508-12
3257241
Immunol Today. 1999 Aug;20(8):347-50
10431153
Eur J Immunol. 1990 Mar;20(3):695-8
2108046
J Biol Chem. 1998 Feb 13;273(7):3838-47
9461564