Stromal Fibroblasts Produce Interleukin-11 in the Colon of TNBS-treated Mice
| Autor: | Takeda, Wakami, Nishina, Takashi, Deguchi, Yutaka, Kawauchi, Mika, Mikami, Tetuo, Yagita, Hideo, Nishiyama, Chiharu, Nakano, Hiroyasu |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | Toho Journal of Medicine. 6(3):111-120 |
| ISSN: | 2189-1990 |
| Popis: | Original Article Introduction: Interleukin (IL) -11 is a member of the IL-6 cytokine family and is implicated to play a role in pleiotropic functions such as hematopoiesis, bone development, tissue repair, and tumor development. Although the protective function of IL-11 in trinitrobenzene sulfonic acid (TNBS)-induced colitis has been reported, whether Il11 expression is induced in the colon of TNBS-treated mice is still unclear. Methods: After inducing TNBS-induced colitis in C57BL/6 mice, Il6 and Il11 expressions in the colon were determined using quantitative PCR. Colonic sections were stained with hematoxylin and eosin (H&E) or immunostained with anti-IL-11 antibody along with antibodies against lineage-specific markers. To assess the contribution of the transforming growth factor (TGF)-β signal or mitogen-activated protein kinase/ERK kinase (MEK)/ERK pathway to upregulation of Il11 expression, we treated mice with TNBS in the presence of neutralizing antibody against TGF-β or a MEK inhibitor, trametinib. Subsequently, Il11 expression in the colon was determined using qPCR. Results: TNBS treatment increased Il11 expression in the colon. Immunohistochemical analysis revealed that IL-11+ cells appeared in the subepithelial tissues of the inflamed colon. IL-11+ cells expressed podoplanin, vimentin, and collagen IV but did not express α-smooth muscle actin, suggesting that these cells were fibroblasts, and not myofibroblasts. Moreover, TNBS administration induced ERK activation in the colon, and the blockade of the MEK/ERK pathway abolished Il11 expression in the colon. Conclusions: Stromal fibroblasts produced IL-11 in the colon of TNBS-treated mice in a MEK/ERK-dependent manner. |
| Databáze: | OpenAIRE |
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