Angiotensin 1-7 ameliorates caerulein-induced inflammation in pancreatic acinar cells by downregulating Toll-like receptor 4/nuclear factor-κB expression

Wang,Yan; Wang,Guoxing; Cui,Lijian; Liu,Ruixia; Xiao,Hongli; Yin,Chenghong

doi:10.3892/mmr.2017.8354

Angiotensin 1-7 ameliorates caerulein-induced inflammation in pancreatic acinar cells by downregulating Toll-like receptor 4/nuclear factor-κB expression

Authors:
- Yan Wang
- Guoxing Wang
- Lijian Cui
- Ruixia Liu
- Hongli Xiao
- Chenghong Yin
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Affiliations: Department of Emergency, Beijing Friendship Hospital, Beijing 100050, P.R. China, Department of Emergency, Beijing Chao‑Yang Hospital, Beijing 100020, P.R. China, Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, P.R. China
Published online on: December 27, 2017 https://doi.org/10.3892/mmr.2017.8354
Pages: 3511-3518
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the effects of angiotensin (Ang) 1-7 on caerulein (CAE)-stimulated nuclear factor (NF)‑κB, Toll‑like receptor (TLR4) and cytokine expression using pancreatic acinar AR42J cells. AR42J cells were treated with 10 nmol/l CAE for various durations. In addition, cells were pretreated with various concentrations of Ang 1‑7 or A779, a specific antagonist of Ang 1‑7, and were stimulated with CAE for 12 h. Control cells were treated with vehicle (F‑12K complete medium with 2% fetal bovine serum, 10 U/ml penicillin and 100 mg/ml streptomycin) alone. The mRNA and protein expression levels of TLR4, NF‑κB, interleukin (IL)‑6, IL‑8, IL‑10 and tumor necrosis factor‑α (TNF‑α) were determined by western blotting, immunofluorescence and reverse transcription‑quantitative polymerase chain reaction. CAE treatment stimulated TLR4 and NF‑κB expression within AR42J cells. Immunofluorescence indicated that TLR4 was expressed on the membranes and in the cytoplasm of AR42J cells, whereas NF‑κB expression accumulated in the cytoplasm and nuclei. CAE‑induced expression of TLR4 and NF‑κB within AR42J cells was abrogated by 10‑5 mmol/l Ang 1‑7; however, TLR4 and NF‑κB expression was enhanced with the addition of A779, particularly 10‑5 mmol/l. In addition, treatment with 10‑6 and 10‑5 mmol/l Ang 1‑7 significantly mitigated CAE‑induced expression of IL‑6, IL‑8 and TNF‑α, whereas it enhanced IL‑10 expression. Conversely, A779 treatment enhanced the CAE‑induced expression of IL‑6, IL‑8 and TNF‑α, and reduced IL‑10 expression in AR42J cells. In conclusion, these results suggested that Ang 1‑7 may attenuate CAE‑induced inflammation by downregulating TLR4, NF‑κB and proinflammatory cytokine expression within AR42J cells. Therefore, Ang 1‑7 may exert protective effects against the pathological progression of AP in a cell model of AP induced by CAE and may be considered in the development of treatments for this disease.

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