TY - JOUR
T1 - Flagellin stimulation suppresses IL-7 secretion of intestinal epithelial cells
AU - Yoshioka, Atsushi
AU - Okamoto, Ryuichi
AU - Oshima, Shigeru
AU - Akiyama, Junko
AU - Tsuchiya, Kiichiro
AU - Nakamura, Tetsuya
AU - Kanai, Takanori
AU - Watanabe, Mamoru
N1 - Funding Information:
This study was supported in part by Grants-in-Aid for Scientific Research, Scientific Research on Priority Areas, Exploratory Research and Creative Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology; The Japanese Ministry of Health, Labor and Welfare; The Japan Medical Association; The Foundation for Advancement of International Science; The Japanese Society of Gastroenterology; Research Fund of Mitsukoshi Health and Welfare Foundation; Research Fund of Japan Intractable Diseases Research Foundation.
PY - 2008/10
Y1 - 2008/10
N2 - IL-7 is a cytokine, which regulates development, maintenance and proliferation of T lymphocytes within the human immune system. Production of IL-7 is observed in a sterile environment such as thymus or bone marrow. However, it is also known that intestinal epithelial cells (IECs) residing in close contact with numerous bacterial stimuli also produce IL-7. Here we show that secretion of IL-7 by IECs is significantly suppressed upon stimulation by various bacterial components, including flagellin. Analysis of the intracellular mechanism by which flagellin regulates IL-7 production revealed that flagellin down-regulates expression of the two major transcripts encoding IL-7. Surprisingly, such function of flagellin was independent from the known transcriptional regulation of the IL-7 gene, as no significant change was observed in the transcriptional activity regulated by the previously identified promoter region. As the stability of IL-7 mRNA also remained unchanged upon flagellin stimulation, results suggested the possible involvement of a yet unknown transcriptional regulation of the IL-7 gene. These results describe a novel regulation of IL-7 production by bacterial stimuli, presumably mediated via Toll-like receptors. The present system might contribute to regulate the local lymphocyte pool, in response to the gut luminal or sub-mucosal bacterial abundance.
AB - IL-7 is a cytokine, which regulates development, maintenance and proliferation of T lymphocytes within the human immune system. Production of IL-7 is observed in a sterile environment such as thymus or bone marrow. However, it is also known that intestinal epithelial cells (IECs) residing in close contact with numerous bacterial stimuli also produce IL-7. Here we show that secretion of IL-7 by IECs is significantly suppressed upon stimulation by various bacterial components, including flagellin. Analysis of the intracellular mechanism by which flagellin regulates IL-7 production revealed that flagellin down-regulates expression of the two major transcripts encoding IL-7. Surprisingly, such function of flagellin was independent from the known transcriptional regulation of the IL-7 gene, as no significant change was observed in the transcriptional activity regulated by the previously identified promoter region. As the stability of IL-7 mRNA also remained unchanged upon flagellin stimulation, results suggested the possible involvement of a yet unknown transcriptional regulation of the IL-7 gene. These results describe a novel regulation of IL-7 production by bacterial stimuli, presumably mediated via Toll-like receptors. The present system might contribute to regulate the local lymphocyte pool, in response to the gut luminal or sub-mucosal bacterial abundance.
KW - Flagellin
KW - IL-7
KW - Intestinal epithelial cells
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U2 - 10.1016/j.cyto.2008.06.004
DO - 10.1016/j.cyto.2008.06.004
M3 - Article
C2 - 18657434
AN - SCOPUS:52949112252
VL - 44
SP - 57
EP - 64
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 1
ER -