Proinflammatory Th2 cytokines induce production of thymic stromal lymphopoietin in human colonic epithelial cells.
OBJECTIVE
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-alpha) and interleukin-4 (IL-4) induced TSLP expression and that TSLP expression by TNF-alpha + IL-4 was further enhanced by either Toll-like receptor 3 ligand or interferon (IFN)-gamma.


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.
Tanaka
Junya
J
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, Japan.
Saga
Kazuyuki
K
Kido
Masahiro
M
Nishiura
Hisayo
H
Akamatsu
Takuji
T
Chiba
Tsutomu
T
Watanabe
Norihiko
N
D000293:Adolescent; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D016022:Case-Control Studies; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000276:immunology / Q000503:physiopathology; D003106:Colon / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000094632:Thymic Stromal Lymphopoietin