A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice.
OBJECTIVE
A CD30-ligand (CD30L) is a 40-kilodalton, type II membrane-associated glycoprotein belonging to the tumor necrosis factor family. Serum levels of soluble CD30 increased in inflammatory bowel diseases (IBD), suggesting that CD30L/CD30 signaling is involved in the pathogenesis of IBD. In this study, we investigated the role of CD30L in oxazolone (OXA)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis in CD30L knockout (KO) mice.


METHODS
Colitis was induced by OXA or TNBS in CD30LKO mice with BALB/c or C57BL/6 background, respectively, and diverse clinical signs of the disease were evaluated. Cytokine production from lamina propria T cells of the colon was assessed by enzyme-linked immunosorbent assay. Anti-interleukin (IL)-4 monoclonal antibody (mAb) or agonistic anti-CD30 mAb was inoculated in mice with colitis induced by OXA or TNBS.


RESULTS
CD30LKO mice were susceptible to OXA-induced colitis but resistant to TNBS-induced acute colitis. The levels of T helper cell 2 type cytokines such as IL-4 and IL-13 in the LP T cells were significantly higher, but the levels of interferon gamma were lower in OXA- or TNBS-treated CD30LKO mice than in wild-type mice. In vivo administration of agonistic anti-CD30 mAb ameliorated OXA-induced colitis but aggravated TNBS-induced colitis in CD30LKO mice.


CONCLUSIONS
These results suggest that CD30L/CD30 signaling is involved in development of both OXA- and TNBS-induced colitis. Modulation of CD30L/CD30 signaling by mAb could be a novel biologic therapy for IBD.
Sun
Xun
X
Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Somada
Shinichi
S
Shibata
Kensuke
K
Muta
Hiromi
H
Yamada
Hisakata
H
Yoshihara
Hirofumi
H
Honda
Kuniomi
K
Nakamura
Kazuhiko
K
Takayanagi
Ryhoichi
R
Tani
Kenzaburo
K
Podack
Eckhard R
ER
Yoshikai
Yasunobu
Y
D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D053285:CD30 Ligand / Q000235:genetics / Q000502:physiology*; D003092:Colitis / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D015847:Interleukin-4 / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D017730:Ki-1 Antigen / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone; D015398:Signal Transduction / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D053285:CD30 Ligand; D016207:Cytokines; D017730:Ki-1 Antigen; D010081:Oxazolone; D015847:Interleukin-4; D014302:Trinitrobenzenesulfonic Acid