Open AccessEffect of short-time treatment with TNF-α on stem cell activity and barrier function in enteroids
Author(s) -
Yuki Saito,
Makoto Shimizu,
Ken Iwatsuki,
Hikaru Hanyu,
Tsuneharu Miki,
Yoshiko Sugita-Konishi,
Kazuo KobayashiHattori
Publication year - 2021
Publication title -
cytotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.488
H-Index - 62
eISSN - 1573-0778
pISSN - 0920-9069
DOI - 10.1007/s10616-021-00487-y
Subject(s) - lgr5 , tumor necrosis factor alpha , microbiology and biotechnology , barrier function , inflammation , stem cell , biology , stem cell marker , progenitor cell , immunology , chemistry , cancer stem cell
Although tumor necrosis factor-α (TNF-α) is a known major inflammatory mediator in inflammatory bowel disease (IBD) and has various effects on intestinal epithelial cell (IEC) homeostasis, the changes in IECs in the early inflammatory state induced during short-time treatment (24 h) with TNF-α remain unclear. In this study, we investigated TNF-α-induced alterations in IECs in the early inflammatory state using mouse jejunal organoids (enteroids). Of the inflammatory cytokines, i.e., TNF-α, IL-1β, IL-6, and IL-17, only TNF-α markedly increased the mRNA level of macrophage inflammatory protein 2 (MIP-2; the mouse homologue of interleukin-8), which is induced in the early stages of inflammation. TNF-α stimulation (3 h and 6 h) decreased the mRNA level of the stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) and polycomb group ring finger 4 and the progenitor cell marker prominin-1, which is also known as CD133. In addition, TNF-α treatment (24 h) decreased the number of Lgr5-positive cells and enteroid proliferation. TNF-α stimulation at 3 h and 6 h also decreased the mRNA level of chromogranin A and mucin 2, which are respective markers of enteroendocrine and goblet cells. Moreover, enteroids treated with TNF-α (24 h) not only decreased the integrity of tight junctions and cytoskeletal components but also increased intercellular permeability in an influx test with fluorescent dextran, indicating disrupted intestinal barrier function. Taken together, our findings indicate that short-time treatment with TNF-α promotes the inflammatory response and decreases intestinal stem cell activity and barrier function.