Human Intestinal Epithelial Cells Express Interleukin-10 through Toll-Like Receptor 4-Mediated Epithelial-Macrophage Crosstalk

被引：65

作者：

Hyun, Jinhee ^{[1
]}

Romero, Laura ^{[1
]}

Riveron, Reldy ^{[1
]}

Flores, Claudia ^{[3
,4
]}

Kanagavelu, Saravana ^{[1
,3
,4
]}

Chung, Kristina D. ^{[1
]}

Alonso, Ana ^{[1
]}

Sotolongo, John ^{[1
]}

Ruiz, Jose ^{[1
]}

Manukyan, Armine ^{[3
,4
]}

Chun, Sally ^{[3
,4
]}

Singh, Gaurav ^{[1
]}

Salas, Pedro ^{[2
]}

Targan, Stephan R. ^{[3
,4
]}

Fukata, Masayuki ^{[1
,2
,3
,4
]}

机构：

[1] Univ Miami, Miller Sch Med, Dept Med, Div Gastroenterol, Miami, FL 33136 USA

[2] Univ Miami, Dept Cell Biol, Miami, FL 33136 USA

[3] Cedars Sinai Med Ctr, F Widjaja Fdn, Dept Med, Div Gastroenterol, Los Angeles, CA 90048 USA

[4] Cedars Sinai Med Ctr, Inflammatory Bowel & Immunol Res Inst, Los Angeles, CA 90048 USA

来源：

JOURNAL OF INNATE IMMUNITY | 2015年 / 7卷 / 01期

关键词：

Epithelial cells; Interleukin-10; Intestine; Macrophages; Peroxisome proliferator-activated receptor; Toll-like receptors; PPAR-GAMMA ACTIVITY; ULCERATIVE-COLITIS; CROHNS-DISEASE; IL-10; ACTIVATION; PROLIFERATION; INFLAMMATION; PERMEABILITY; PATHOGENESIS; CONTRIBUTE;

D O I：

10.1159/000365417

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

In the intestine, interaction between epithelial cells and macrophages (M Phi s) create a unique immunoregulatory microenvironment necessary to maintain local immune and tissue homeostasis. Human intestinal epithelial cells (IECs) have been shown to express interleukin (IL)-10, which keeps epithelial integrity. We have demonstrated that bacterial signaling through Toll-like receptor (TLR) 4 induces 15-deoxy-Delta-12,14-prostaglandin J2 (15d-PGJ2) synthesis in intestinal M Phi s by cyclooxygenase (Cox)-2 expression. Here, we show that TLR4 signaling generates crosstalk between IECs and M Phi s that enhances IL-10 expression in IECs. Direct stimulation of TLR4 leads to the expression of IL-10 in IECs, while the presence of M Phi s in a Transwell system induces another peak in IL-10 expression in IECs at a later time point. The second peak of the IL-10 expression is two times greater than the first peak. This late induction of IL-10 depends on the nuclear receptor peroxisome proliferator-activated receptor (PPAR). that is accumulated in IECs by TLR4-mediated inhibition of the ubiquitin-proteasomal pathway. TLR4 signaling in M Phi s in turn synthesizes 15d-PGJ2 through p38 and ERK activation and Cox-2 induction, which activates PPAR. in IECs. These results suggest that TLR4 signaling maintains IL-10 production in IECs by generating epithelial-M Phi s crosstalk, which is an important mechanism in the maintenance of intestinal homeostasis mediated through host-bacterial interactions. (C) 2014 S. Karger AG, Basel

引用

页码：87 / 101

页数：15

共 49 条

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