Single dose of OCH improves mucosal T helper type 1/T helper type 2 cytokine balance and prevents experimental colitis in the presence of valpha14 natural killer T cells in mice.
OBJECTIVE
Valpha14 natural killer T (NKT) cells seem to play important roles in the development of various autoimmune diseases. However, the pathophysiologic role of NKT cells in inflammatory bowel disease remains unclear. To clarify the mechanism by which the activation of NKT cells mediates protection against intestinal inflammation, we investigated the antiinflammatory role of specifically activated Valpha14 NKT cells by glycolipids in a mouse experimental model of colitis induced by dextran sulfate sodium (DSS).


METHODS
Colitis was induced in C57BL/6 mice by the oral administration of 1.5% DSS for 9 days. A single dose of OCH or alpha-galactosylceramide, a ligand for NKT cells, was administered on day 3 after the induction of colitis. Body weights and colonic mucosal injury were assessed in each glycolipid-treated group. Interferon-gamma and interleukin-4 levels in the supernatants from colonic lamina propria lymphocytes (LPLs) were measured by enzyme-linked immunosorbent assay.


RESULTS
The administration of a single dose of OCH attenuated colonic inflammation, as defined by body weights and histologic injury. The protective effects of OCH could not be observed in Valpha14 NKT cell-deficient mice. In vivo treatment with OCH had improved the interferon-gamma/interleukin-4 ratio from colonic LPLs on day 9 after DSS treatment.


CONCLUSIONS
The present data indicated that the activation of Valpha14 NKT cells by OCH plays a pivotal role in mediating intestinal inflammation via altered mucosal T-helper type 1/type 2 responses. Therapeutic strategies that are designed to activate specifically Valpha14 NKT cells may prove to be beneficial in treating intestinal inflammation.
Ueno
Yoshitaka
Y
Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan.
Tanaka
Shinji
S
Sumii
Masaharu
M
Miyake
Sachiko
S
Tazuma
Susumu
S
Taniguchi
Masaru
M
Yamamura
Takashi
T
Chayama
Kazuaki
K
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage; D003092:Colitis / Q000276:immunology* / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D006017:Glycolipids / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D015847:Interleukin-4 / Q000032:analysis / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000998:Antiviral Agents; D006017:Glycolipids; D015847:Interleukin-4; D007371:Interferon-gamma; D016264:Dextran Sulfate