Digestive Diseases and Sciences

, Volume 55, Issue 7, pp 1896–1904 | Cite as

Proinflammatory Th2 Cytokines Induce Production of Thymic Stromal Lymphopoietin in Human Colonic Epithelial Cells

  • Junya Tanaka
  • Kazuyuki Saga
  • Masahiro Kido
  • Hisayo Nishiura
  • Takuji Akamatsu
  • Tsutomu Chiba
  • Norihiko Watanabe
Original Article

Abstract

Purpose

Thymic stromal lymphopoietin (TSLP) is released by intestinal epithelial cells (IECs), and TSLP-conditioned dendritic cells appear to be involved in immune homeostasis of intestine and immunoglobulin A (IgA) class-switching in the physiological condition. In contrast, TSLP activates dendritic cells to induce strong T-cell proliferation and is involved in inflammatory T helper (Th) 2 responses in human allergic diseases. However, it is not clear how TSLP production by IECs is regulated in ulcerative colitis (UC), which appears to involve inflammatory Th2 responses. The aim of this study is to examine how TSLP production by IECs is regulated in ulcerative colitis.

Results

We show here that expression of TSLP was enhanced in mucosal lesions from UC patients in which inflammatory Th2 cytokine production was predominant. In addition, using a human colonic epithelial cell line, we demonstrated that a combination of tumor necrosis factor-alpha (TNF-α) and interleukin-4 (IL-4) induced TSLP expression and that TSLP expression by TNF-α + IL-4 was further enhanced by either Toll-like receptor 3 ligand or interferon (IFN)-γ.

Conclusions

Taken together, as in human allergic diseases, an inflammatory Th2 condition in the mucosal lesions of UC patients may trigger increased TSLP expression by IECs, resulting in exacerbation of UC.

Keywords

TSLP Ulcerative colitis Interleukin-4 Tumor necrosis factor-α Interferon-γ Toll-like receptor 3 ligand 

Abbreviations

APRIL

A proliferation-inducing ligand

DC

Dendritic cell

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

IBD

Inflammatory bowel disease

IFN-γ

Interferon-γ

IL

Interleukin

IECs

Intestinal epithelial cells

RT-PCR

Reverse-transcription polymerase chain reaction

Th

T helper

TLR

Toll-like receptor

TLR-L

Toll-like receptor-ligand

TSLP

Thymic stromal lymphopoietin

TNF-α

Tumor necrosis factor-α

UC

Ulcerative colitis

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Junya Tanaka
    • 1
    • 2
  • Kazuyuki Saga
    • 1
    • 2
  • Masahiro Kido
    • 1
    • 2
  • Hisayo Nishiura
    • 1
    • 2
  • Takuji Akamatsu
    • 1
    • 2
  • Tsutomu Chiba
    • 1
  • Norihiko Watanabe
    • 1
    • 2
  1. 1.Department of Gastroenterology and Hepatology, Graduate School of MedicineKyoto UniversityKyotoJapan
  2. 2.Center for Innovation in Immunoregulative Technology & Therapeutics, Graduate School of MedicineKyoto UniversityKyotoJapan

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