Coculture with bone marrow‑derived mesenchymal stem cells attenuates inflammation and apoptosis in lipopolysaccharide‑stimulated alveolar epithelial cells via enhanced secretion of keratinocyte growth factor and angiopoietin‑1 modulating the Toll‑like receptor‑4 signal pathway

Chen,Xu‑Xin; Tang,Lu; Han,Zhi‑Hai; Wang,Wen‑Jing; Meng,Ji‑Guang

doi:10.3892/mmr.2019.9836

Coculture with bone marrow‑derived mesenchymal stem cells attenuates inflammation and apoptosis in lipopolysaccharide‑stimulated alveolar epithelial cells via enhanced secretion of keratinocyte growth factor and angiopoietin‑1 modulating the Toll‑like receptor‑4 signal pathway

Authors:
- Xu‑Xin Chen
- Lu Tang
- Zhi‑Hai Han
- Wen‑Jing Wang
- Ji‑Guang Meng
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Affiliations: Department of Respiratory Medicine, Navy General Hospital of The People's Liberation Army, Beijing 100037, P.R. China, Department of Neurology, The First Hospital of Changsha, Changsha, Hunan 430100, P.R. China, Cardiothoracic Surgery Intensive Care Unit, Anqing Municipal Hospital, Anqing, Anhui 246003, P.R. China
Published online on: January 8, 2019 https://doi.org/10.3892/mmr.2019.9836
Pages: 1891-1902

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Abstract

Acute lung injury (ALI) is a common, costly and potentially lethal disease with characteristics of alveolar‑capillary membrane disruption, pulmonary edema and impaired gas exchange due to increased apoptosis and pulmonary inflammation. There is no effective and specific therapy for ALI; however, mesenchymal stem cells (MSCs) have been demonstrated to be a potential option. Lipopolysaccharide (LPS) is a highly proinflammatory molecule that is used to mimic an in vivo inflammatory and damaged state in vitro. The present study investigated the effect of bone marrow‑derived MSCs on an LPS‑induced alveolar epithelial cell (A549 cell line) injury and its underlying mechanisms by a Transwell system. It was identified that a high LPS concentration caused a decrease in cell viability, increases in apoptosis, inflammatory cytokine release and NF‑κB activity, disruption of the caspase‑3/Bcl‑2 ratio, upregulation of Toll‑like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and toll‑interleukin‑1 receptor domain‑containing adaptor inducing interferon (TRIF) expression, and facilitation of TLR4/MyD88 and TLR4/TRIF complex formation in A549 cells. Coculture with MSCs attenuated all of these activities induced by LPS in A549 cells. In addition, an increased level of keratinocyte growth factor (KGF) and angiopoietin‑1 (ANGPT1) secretion from MSCs was observed under inflammatory stimulation. KGF and/or ANGPT1 neutralizing antibodies diminished the beneficial effect of MSC conditioned medium. These data suggest that MSCs alleviate inflammatory damage and cellular apoptosis induced by LPS in A549 cells by modulating TLR4 signals. These changes may be partly associated with an increased secretion of KGF and ANGPT1 from MSCs under inflammatory conditions. These data provide the basis for development of MSC‑based therapies for ALI.

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