ReferenceID 5192
Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling
Int J Mol Sci
Pulmonary fibrosis is a disease in which lung tissues become fibrous and thereby causes severe respiratory disturbances. Various stimuli induce infiltration of macrophages to the respiratory tract, secreting inflammatory
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- Reference Id
- 5192
- Evidence Id
- 21782
- Core Evidence Id
- 21782
- Source Reference Id
- 3671
- Herb2 Reference Id
- HBREF004468
- Subject Paper Key
- HBIN025796_32752252
- Pubmed Id
- 32752252
- Doi
- 10.3390/ijms21155518
- Paper Title
- Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling
- Paper Abstract
- Pulmonary fibrosis is a disease in which lung tissues become fibrous and thereby causes severe respiratory disturbances. Various stimuli induce infiltration of macrophages to the respiratory tract, secreting inflammatory cytokines, which subsequently leads to the development of pulmonary fibrosis. Aesculetin, a major component of the sancho tree and chicory, is known to biologically have antioxidant and anti-inflammatory effects. Human alveolar epithelial A549 cells were cultured for 24 h in conditioned media of THP-1 monocyte-derived macrophages (mCM) with 1-20 muM aesculetin. Micromolar aesculetin attenuated the cytotoxicity of mCM containing inflammatory tumor necrosis factor-alpha (TNF)-alpha and interleukin (IL)-8 as major cytokines. Aesculetin inhibited alveolar epithelial induction of the mesenchymal markers in mCM-exposed/IL-8-loaded A549 cells ( 47-51% inhibition), while epithelial markers were induced in aesculetin-treated cells subject to mCM/IL-8 ( 1.5-2.3-fold induction). Aesculetin added to mCM-stimulated A549 cells abrogated the collagen production and alveolar epithelial CXC-chemokine receptor 2 (CXCR2) induction. The production of matrix metalloproteinase (MMP) proteins in mCM-loaded A549 cells was reduced by aesculetin ( 52% reduction), in parallel with its increase in tissue inhibitor of metalloproteinases (TIMP) proteins ( 1.8-fold increase). In addition, aesculetin enhanced epithelial induction of tight junction proteins in mCM-/IL-8-exposed cells ( 2.3-2.5-fold induction). The inhalation of polyhexamethylene guanidine (PHMG) in mice accompanied neutrophil predominance in bronchoalveolar lavage fluid (BALF) and macrophage infiltration in alveoli, which was inhibited by orally administrating aesculetin to mice. Treating aesculetin to mice alleviated PHMG-induced IL-8-mediated subepithelial fibrosis and airway barrier disruption. Taken together, aesculetin may antagonize pulmonary fibrosis and alveolar epithelial barrier disruption stimulated by the infiltration of monocyte-derived macrophages, which is typical of PHMG toxicity, involving interaction of IL-8 and CXCR2. Aesculetin maybe a promising agent counteracting macrophage-mediated inflammation-associated pulmonary disorders.
- Journal
- Int J Mol Sci
- Publish Year
- 2020
- Experiment Subject
- mouse; human; aesculetin-treated cells; human alveolar epithelial a549 cells; mcm-/il-8-exposed cells; mcm-exposed/il-8-loaded a549 cells; mcm-loaded a549 cells; mcm-stimulated a549 cells; thp-1 monocyte-derived macrophages
- Experiment Type
- Cell Experiment
- Phenotype Related
- Respiratory Disturbances; Pulmonary Fibrosis; Tumor; Subepithelial Fibrosis; Pulmonary Disorders
- Paper Title Cn
- Paper Title En
- Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling
- Bilingual Status
- semi_complete