sTLR4/sMD‑2 complex alleviates LPS‑induced acute lung injury by inhibiting pro‑inflammatory cytokines and chemokine CXCL1 expression

Meng,Jie; Zou,Yan; Chen,Jifei; Qin,Fengxian; Chen,Xiang; Chen,Xiaoli; Dai,Shengming

doi:10.3892/etm.2018.6746

sTLR4/sMD‑2 complex alleviates LPS‑induced acute lung injury by inhibiting pro‑inflammatory cytokines and chemokine CXCL1 expression

Authors:
- Jie Meng
- Yan Zou
- Jifei Chen
- Fengxian Qin
- Xiang Chen
- Xiaoli Chen
- Shengming Dai
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Affiliations: Medical Science Laboratory, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, P.R. China
Published online on: September 17, 2018 https://doi.org/10.3892/etm.2018.6746
Pages: 4632-4638
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Activation of Toll‑like receptor 4 (TLR4) and its accessory proteins myeloid differentiation protein 2 (MD‑2) can trigger immune and inflammatory activities, and contribute to developing chronic inflammatory diseases. The formation of the TLR4/MD‑2 complex after binding to lipopolysaccharide (LPS) leads to the activation of downstream signaling pathway. The present study was designed to reveal the effect of the soluble form of the extracellular TLR4 domain and MD‑2 (sTLR4/sMD‑2) complex lacking the intracellular and transmembrane domains on various aspects of LPS‑induced inflammation in vivo and in vitro. It was demonstrated that the sTLR4/sMD‑2 complex inhibited the LPS‑induced production of tumor necrosis factor‑α, interleukin‑8 and C‑X‑C motif chemokine ligand 1 (CXCL1) in THP‑1 cells. In addition, it was revealed that the sTLR4/sMD‑2 complex significantly reduced LPS‑induced acute lung injury (ALI) with a reduction of total cells and neutrophil count, pro‑inflammatory cytokines and chemokine CXCL1 in bronchoalveolar lavage fluid. Moreover, the sTLR4/sMD‑2 complex inhibited the number of inflammatory cells in the lung of treated animals. These novel mechanisms emphasized the important role of sTLR4/sMD‑2 complex in ALI and suggested sTLR4/sMD‑2 complex could provide an anti‑inflammatory strategy for treating inflammatory diseases.

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