Enhancement of ICAM-1 via the JAK2/STAT3 signaling pathway in a rat model of severe acute pancreatitis-associated lung injury

Han,Xiao; Wang,Yuxi; Chen,Hailong; Zhang,Jingwen; Xu,Caiming; Li,Jian; Li,Mingyue

doi:10.3892/etm.2016.2988

Enhancement of ICAM-1 via the JAK2/STAT3 signaling pathway in a rat model of severe acute pancreatitis-associated lung injury

Authors:
- Xiao Han
- Yuxi Wang
- Hailong Chen
- Jingwen Zhang
- Caiming Xu
- Jian Li
- Mingyue Li
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116023, P.R. China
Published online on: January 13, 2016 https://doi.org/10.3892/etm.2016.2988
Pages: 788-796
Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute lung injury (ALI), which is associated with severe acute pancreatitis (SAP), results from damage to the pulmonary microvascular endothelial cells (PMVECs), which in turn leads to high levels of inflammatory cytokines that destroy PMVECs. However, the molecular mechanisms underlying SAP‑associated ALI (SAP-ALI) are currently not well understood. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the persistent migration and accumulation of neutrophils and macrophages, which in turn has been associated with the increased permeability of microvascular endothelial cells. Signal transduction via the Janus kinase‑2 (JAK2)/signal transducer and activator of transcription‑3 (STAT3) transcription factors has been shown to be involved in inflammation. The present study aimed to investigate the expression levels of ICAM‑1 and JAK2/STAT3 signaling components in a rat model of SAP‑ALI. SAP was induced in the rat model, and dexamethasone (DEX) was administered to the treatment group. Subsequently, ICAM‑1, interleukin (IL)‑6, IL‑8, tumor necrosis factor (TNF)‑α, JAK2, STAT3 and nuclear factor (NF)‑κB mRNA expression levels were determined using reverse transcription‑polymerase chain reaction; ICAM‑1 protein expression levels were determined using western blotting; and IL‑6, IL‑8 and TNF‑α levels were measured via an enzyme‑linked immunosorbent assay. In addition, an immunohistochemical analysis of ICAM‑1, NF‑κB, JAK2 and STAT3 was conducted, and the protein expression and cell morphology of the lungs in all rats was analyzed. ICAM‑1 mRNA and protein expression levels were significantly increased following induction of SAP, and were significantly decreased in the DEX‑treated group. Furthermore, treatment with DEX significantly reduced serum expression levels of IL‑6, IL‑8 and TNF‑α and decreased expression levels of NF‑κB, JAK2 and STAT3 in the lung tissue, as compared with the untreated SAP group. The present study demonstrated that DEX treatment was able to suppress ICAM‑1 mRNA and protein expression in a rat model of SAP‑ALI via the inhibition of IL-6 and TNF-α-induced JAK2/STAT3 activation; thus suggesting that DEX treatment may be considered a potential strategy in the treatment of patients with SAP-ALI.

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