Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling
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. A...
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/15/5518 |
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| author | Su Yeon Oh Yun-Ho Kim Min-Kyung Kang Eun-Jung Lee Dong Yeon Kim Hyeongjoo Oh Soo-Il Kim Woojin Na Young-Hee Kang |
| author_facet | Su Yeon Oh Yun-Ho Kim Min-Kyung Kang Eun-Jung Lee Dong Yeon Kim Hyeongjoo Oh Soo-Il Kim Woojin Na Young-Hee Kang |
| author_sort | Su Yeon Oh |
| collection | DOAJ |
| description | 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 μM aesculetin. Micromolar aesculetin attenuated the cytotoxicity of mCM containing inflammatory tumor necrosis factor-α (TNF)-α 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. |
| first_indexed | 2024-03-10T18:02:02Z |
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| language | English |
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| spelling | doaj.art-45550dc50838404983db5e1bebd6f1f42023-11-20T08:47:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012115551810.3390/ijms21155518Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 SignalingSu Yeon Oh0Yun-Ho Kim1Min-Kyung Kang2Eun-Jung Lee3Dong Yeon Kim4Hyeongjoo Oh5Soo-Il Kim6Woojin Na7Young-Hee Kang8Department of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition and The Korean Institute of Nutrition, Hallym University, Chuncheon 24252, KoreaPulmonary 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 μM aesculetin. Micromolar aesculetin attenuated the cytotoxicity of mCM containing inflammatory tumor necrosis factor-α (TNF)-α 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.https://www.mdpi.com/1422-0067/21/15/5518aesculetinalveolar cellsinflammationinterleukin-8macrophagespolyhexamethylene guanidine |
| spellingShingle | Su Yeon Oh Yun-Ho Kim Min-Kyung Kang Eun-Jung Lee Dong Yeon Kim Hyeongjoo Oh Soo-Il Kim Woojin Na Young-Hee Kang Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling International Journal of Molecular Sciences aesculetin alveolar cells inflammation interleukin-8 macrophages polyhexamethylene guanidine |
| title | Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling |
| title_full | Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling |
| title_fullStr | Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling |
| title_full_unstemmed | Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling |
| title_short | Aesculetin Attenuates Alveolar Injury and Fibrosis Induced by Close Contact of Alveolar Epithelial Cells with Blood-Derived Macrophages via IL-8 Signaling |
| title_sort | aesculetin attenuates alveolar injury and fibrosis induced by close contact of alveolar epithelial cells with blood derived macrophages via il 8 signaling |
| topic | aesculetin alveolar cells inflammation interleukin-8 macrophages polyhexamethylene guanidine |
| url | https://www.mdpi.com/1422-0067/21/15/5518 |
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