Interleukin-17 as a Therapy Target in Intestinal Fibrosis
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Interleukin‑17 as a Therapy Target in Intestinal Fibrosis Bao‑Lei Zhang1 · Tang‑Shuai Liang1 · Dao‑Gui Yang1 Received: 26 June 2020 / Accepted: 7 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
To the Editors, I read with interest the article by Li et al. [1] revealing that interleukin (IL)-17, a newly discovered profibrogenic cytokine, is upregulated in serum and colonic tissues in the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced chronic intestinal fibrosis and anti-IL-17 treatment may weaken this effect. They further show that IL-17 contributes to the pathogenesis of intestinal fibrosis, by down-regulating expression of profibrogenic cytokines and disturbing the matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP)s balance, which indicates these are important for the development of intestinal fibrosis. Although this novel discovery opens the door for new treatment of intestinal fibrosis, it is not known whether IL-17 deficiency or inhibition suppresses the development of intestinal fibrosis only through the interfering with the MMP/TIMPs balance or down-regulating expression of profibrogenic cytokines and whether genetic deletion or pharmaceutical inhibition of IL-17 could produce unwanted side effects. Interestingly, one recent study demonstrated a similar function of IL-17 in intestinal fibrosis. The study demonstrated that IL-17 driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of hydrogen peroxide-inducible clone 5 (HIC-5). They further showed that Itch ubiquitinates is a downstream effector of IL-17 and negatively regulates IL-17 triggered fibrosis [2]. Another animal study showed that IL-17 potentially regulating the RANKL/OPG and MMP/TIMP systems in cardiac fibrosis [3]. Along this line, it would be interesting to find out whether targeting IL-17 suppresses the development of intestinal fibrosis through Itch ubiquitinates or RANKL/OPG and MMP/TIMP signaling pathway?
* Dao‑Gui Yang [email protected] 1
Department of Gastrointestinal Surgery, Liaocheng People’s Hospital and Clinical School of Taishan Medical University, Liaocheng 252000, People’s Republic of China
Zhou et al. [4] observed that “medulloblastoma growth in IL-17-injected mice was significantly inhibited compared to the non-IL-17 treated mice. In contrast to the IL-17 antitumor activity observed in mice injected with splenocytes, we observed that IFN-gamma, IL-6, IL-23, Ccl2, and Ccl20 proteins were significantly increased in tumor tissues of mice injected with IL-17.” These observations demonstrated that IL-17 plays a potential role in the anti-tumor activity of splenocytes. More important, a previous study has demonstrated that endogenous IL-17 contributes to reduce tumor growth and metastasis [5]. For clinical application, the desired approach is to modulate IL-17 expression to attenuate intestinal fibrosis without inducing unwanted side effects in other organs. Thus, it would be interesting to know whether the anti-IL-17approach is safe in
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