The interplay of BMP4 and IL‑7 regulates the apoptosis of intestinal intraepithelial lymphocytes under conditions of ischemia̸reperfusion

Luo,Binyu; Chen,Kang; Feng,Qi; Xiao,Weidong; Ma,Dan; Yang,Hua; Zhang,Chaojun

doi:10.3892/ijmm.2018.3480

The interplay of BMP4 and IL‑7 regulates the apoptosis of intestinal intraepithelial lymphocytes under conditions of ischemia̸reperfusion

Authors:
- Binyu Luo
- Kang Chen
- Qi Feng
- Weidong Xiao
- Dan Ma
- Hua Yang
- Chaojun Zhang
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Affiliations: Department of General Surgery Two, Nanchong Central Hospital, The Second Clinical College of North Sichuan Medical University, Nanchong, Sichuan 637000, P.R. China, Department of General Surgery, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China
Published online on: February 9, 2018 https://doi.org/10.3892/ijmm.2018.3480
Pages: 2640-2650
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The number and function of intestinal intraepithelial lymphocytes (IELs) have been found to be significantly reduced following induction of acute intestinal mucosal damage via intestinal ischemia̸reperfusion (I̸R). However, the mechanism underlying this reduction remains unclear. Therefore, it was hypothesized that the interplay of bone morphogenetic protein (BMP)4 and interleukin (IL)‑7 regulates IEL function and number. Recent studies have demonstrated that the different components of the BMP2̸4 signaling pathway are expressed in intestinal epithelial cells (IECs) via the activation of nuclear factor (NF)‑κB. In the present study, reverse transcription‑polymerase chain reaction analysis and flow cytometry demonstrated that IELs express BMP receptors (BMPRIA, BMPRIB, ActRIA and BMPRII) and non‑canonical signal transduction molecules (NF‑κB). an in vivo mouse intestinal I̸R model was used, and I̸R was shown to increase the expression of BMP4 in IECs and upregulate the expression levels of BMPRIA, BMPRIB and phosphorylated NF‑κB in IELs. Following isolation and culture of IELs, it was observed that exogenous BMP4 also upregulated the expression of BMPRIA and BMPRIB and activated NF‑κB signaling in IELs, inducing IEL apoptosis. In addition, the rate of apoptosis of IELs decreased following treatment with the BMP‑specific antagonist Noggin or with the NF‑κB inhibitor pyrrolidine dithiocarbamate. Furthermore, it was observed that exogenous IL‑7 can decrease BMP4 protein expression in IECs and the expression of phosphorylated NF‑κB protein in IELs. The findings of the present study suggest that, under conditions of I̸R, IEC‑derived BMP4 activates NF‑κB signaling in IELs, inducing IEL apoptosis, further aggravating the dysfunction of the intestinal mucosal barrier. However, these effects may be alleviated by IL‑7 treatment. Therefore, BMP4 and IL‑7 appear to be involved in the interaction between IECs and IELs and in the mechanism underlying intestinal mucosal barrier dysfunction.

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