Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent.
BACKGROUND
Curcumin (diferulolylmethane) has been shown to have a protective role in mouse models of inflammatory bowel diseases (IBD) and to reduce the relapse rate in human ulcerative colitis (UC), thus making it a potentially viable supportive treatment option. Trinitrobenzene sulfonic acid (TNBS) colitis in NKT-deficient SJL/J mice has been described as Th1-mediated inflammation, whereas BALB/c mice are believed to exhibit a mixed Th1/Th2 response.


METHODS
We therefore investigated the effect of dietary curcumin in colitis induced in these 2 strains.


RESULTS
In the BALB/c mice, curcumin significantly increased survival, prevented weight loss, and normalized disease activity. In the SJL/J mice, curcumin demonstrated no protective effects. Genomewide microarray analysis of colonic gene expression was employed to define the differential effect of curcumin in these 2 strains. This analysis not only confirmed the disparate responses of the 2 strains to curcumin but also indicated different responses to TNBS. Curcumin inhibited proliferation of splenocytes from naive BALB/c mice but not SJL/J mice when nonspecifically stimulated in vitro with concanavalin A (ConA). Proliferation of CD4(+) splenocytes was inhibited in both strains, albeit with about a 2-fold higher IC(50) in SJL/J mice. Secretion of IL-4 and IL-5 by CD4(+) lymphocytes of BALB/c mice but not SJL/J mice was significantly augmented by ConA and reduced to control levels by curcumin.


CONCLUSIONS
The efficacy of dietary curcumin in TNBS colitis varies in BALB/c and SJL/J mouse strains. Although the exact mechanism underlying these differences is unclear, the results suggest that the therapeutic value of dietary curcumin may differ depending on the nature of immune dysregulation in IBD.
Billerey-Larmonier
Claire
C
Department of Pediatrics, Steele Children's Research Center, University of Arizona Health Sciences Center, Tucson 85724, USA.
Uno
Jennifer K
JK
Larmonier
Nicolas
N
Midura
Anna J
AJ
Timmermann
Barbara
B
Ghishan
Fayez K
FK
Kiela
Pawel R
PR
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D003208:Concanavalin A / Q000494:pharmacology; D003474:Curcumin / Q000008:administration & dosage*; D004032:Diet; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D014302:Trinitrobenzenesulfonic Acid
D003208:Concanavalin A; D014302:Trinitrobenzenesulfonic Acid; D003474:Curcumin