TY - JOUR
T1 - A Critical Role of CD30 Ligand/CD30 in Controlling Inflammatory Bowel Diseases in Mice
AU - Sun, Xun
AU - Somada, Shinichi
AU - Shibata, Kensuke
AU - Muta, Hiromi
AU - Yamada, Hisakata
AU - Yoshihara, Hirofumi
AU - Honda, Kuniomi
AU - Nakamura, Kazuhiko
AU - Takayanagi, Ryhoichi
AU - Tani, Kenzaburo
AU - Podack, Eckhard R.
AU - Yoshikai, Yasunobu
N1 - Funding Information:
Supported, in part, by the Program of Founding Research Centers for Emerging and Reemerging Infectious Diseases (launched as a project commissioned by the Ministry of Education, Culture, Sports, Science and Technology [MEXT], Japan); a Grant-in-Aid for Scientific Research on Priority Areas, Japan Society for the Promotion of Science; and by grants from the Japanese Ministry of Education, Science and Culture (to Y.Y.).
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2008/2
Y1 - 2008/2
N2 - Background & Aims: 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 γ 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.
AB - Background & Aims: 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 γ 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.
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U2 - 10.1053/j.gastro.2007.11.004
DO - 10.1053/j.gastro.2007.11.004
M3 - Article
C2 - 18242212
AN - SCOPUS:38649135387
VL - 134
SP - 447-458.e3
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 2
ER -