NOD receptor and TLR9 modulation in severe acute pancreatitis‑induced intestinal injury

Yan,Yupeng; Lu,Bin; Li,Pengyang; Wang,Ji

doi:10.3892/mmr.2017.7661

NOD receptor and TLR9 modulation in severe acute pancreatitis‑induced intestinal injury

Authors:
- Yupeng Yan
- Bin Lu
- Pengyang Li
- Ji Wang
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Affiliations: Intensive Care Unit, China Meitan General Hospital, Beijing 100028, P.R. China, Department of Anesthesiology, Beijing Hospital of Traditional Chinese Medicine, Beijing 100010, P.R. China, Department of Orthopedics, Dongzhimen Hospital, Beijing 100010, P.R. China
Published online on: September 29, 2017 https://doi.org/10.3892/mmr.2017.7661
Pages: 8471-8476

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Abstract

Severe acute pancreatitis (SAP) has a rapid onset and may cause multiple organ dysfunction syndrome (MODS), which has high mortality. Nucleotide binding oligomerization domain (NOD) receptor and Toll‑like receptor 9 (TLR9), a pattern recognition receptor in innate immunity, are involved in inflammation, immunity and pathogen recognition. The role and mechanism of the NOD receptor and TLR9 in early MODS of SAP‑induced intestinal injury, however, remain unclear. Wistar rats were divided into control, SAP, TLR9 inhibitor and NOD receptor activation groups. Reverse transcription‑quantitative polymerase chain reaction was used to analyze the expression of TLR9, NOD1 and NOD2 in the experimental treatment groups. Serum amylase, creatinine and alanine aminotransferase indices were measured, ELISA was used to determine the expression of tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) and western blot analysis was used to assess nuclear factor (NF)‑κB expression levels in intestinal tissues. Reactive oxygen species (ROS) levels and superoxide dismutase (SOD) activity were quantified by spectrometry. SAP and NOD receptor activation groups exhibited significantly elevated TLR9, NOD1, NOD2, TNF‑α, IL‑1β and nuclear factor (NF)‑κB levels compared with the control group. Furthermore, ROS production was increased, SOD activity was decreased and higher serum indices were exhibited, compared with the control group. The NOD receptor group presented more significant differences compared with the SAP group. The TLR9 inhibitor group exhibited opposite effects, with markedly decreased TLR9, NOD1, NOD2, TNF‑α, IL‑1β and NF‑κB levels. The TLR9 inhibitor group also presented reduced ROS production, increased SOD activity and lower serum indexes compared to the SAP group. The present study therefore indicated that NOD receptor and TLR9 may modulate the inflammatory response and further impact upon intestinal injury of SAP, via the regulation of NF‑κB expression and the oxidation/antioxidation balance, suggesting therapeutically targeting NOD receptor and TLR9 might be a useful approach for the treatment of severe acute pancreatitis.

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