Protective Roles of CX3CR1-Mediated Signals in Toxin A-Induced Enteritis through the Induction of Heme Oxygenase-1 Expression

被引：25

作者：

Inui, Masanori ^{[2
]}

Ishida, Yuko ^{[1
]}

Kimura, Akihiko ^{[1
]}

Kuninaka, Yumi ^{[1
]}

Mukaida, Naofumi ^{[3
]}

Kondo, Toshikazu ^{[1
]}

机构：

[1] Wakayama Med Univ, Dept Forens Med, Sch Med, Wakayama 6418509, Japan

[2] Wakayama Med Univ, Dept Immunol, Sch Med, Inst Adv Med, Wakayama 6418509, Japan

[3] Kanazawa Univ, Canc Res Inst, Div Mol Bioregulat, Kanazawa, Ishikawa 920, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2011年 / 186卷 / 01期

关键词：

CLOSTRIDIUM-DIFFICILE TOXIN; FRACTALKINE RECEPTOR CX(3)CR1; INTESTINAL EPITHELIAL-CELLS; CHEMOKINE RECEPTOR; CC-CHEMOKINE; ESSENTIAL INVOLVEMENT; SEPTIC PERITONITIS; HUMAN MONOCYTES; KNOCKOUT MICE; HOST-DEFENSE;

D O I：

10.4049/jimmunol.1000043

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The injection of Clostridium difficile toxin A into the ileal loops caused fluid accumulation with the destruction of intestinal epithelial structure and the recruitment of neutrophils and macrophages. Concomitantly, intraileal gene expression of CX3CL1/fractalkine (FKN) and its receptor, CX3CR1, was enhanced. When treated with toxin A in a similar manner, CX3CR1-deficient (CX3CR1(-/-)) mice exhibited exaggerated fluid accumulation, histopathological alterations, and neutrophil recruitment, but not macrophage infiltration. Mice reconstituted with CX3CR1(-/-) mouse-derived bone marrow cells exhibited exacerbated toxin A-induced enteritis, indicating that the lack of the CX3CR1 gene for hematopoietic cells aggravated toxin A-induced enteritis. A heme oxygenase-1 (HO-1) inhibitor, tin-protoporphyrin-IX, markedly increased fluid accumulation in toxin A-treated wild-type mice, indicating the protective roles of HO-1 in this situation. HO-1 expression was detected mainly in F4/80-positive cells expressing CX3CR1, and CX3CR1(-/-) mice failed to increase HO-1 expression after toxin A treatment. Moreover, CX3CL1/FKN induced HO-1 gene expression by isolated lamina propria-derived macrophages or a mouse macrophage cell line, RAW264.7, through the activation of the ERK signal pathway. Thus, CX3CL1/FKN could induce CX3CR1-expressing macrophages to express HO-1, thereby ameliorating toxin A-induced enteritis. The Journal of Immunology, 2011, 186: 423-431.

引用

页码：423 / 431

页数：9

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