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PM2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway.
Part Fibre Toxicol. 2018 01 12; 15(1):4.PF

Abstract

BACKGROUND

Epidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo.

RESULT

The cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3. Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11-7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells. In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice. Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects.

CONCLUSION

These results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway.

Authors+Show Affiliations

Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec 1, Ren-Ai Road, Taipei, Taiwan.Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec 1, Ren-Ai Road, Taipei, Taiwan.Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec 1, Ren-Ai Road, Taipei, Taiwan.Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec 1, Ren-Ai Road, Taipei, Taiwan.Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec 1, Ren-Ai Road, Taipei, Taiwan.Department of Family Medicine, College of Medicine and Hospital, Taipei, Taiwan. Center for Complementary and Integrated Medicine, National Taiwan University Hospital, Taipei, Taiwan.Department of Internal Medicine, Taoyuan General Hospital, Department of Health and Welfare, No.1492, Zhongshan Road, Taoyuan, Taiwan.Department of Microbiology and Immunology, National Cheng Kung University, Tainan, Taiwan.Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.Department of Internal Medicine, Taoyuan General Hospital, Department of Health and Welfare, No.1492, Zhongshan Road, Taoyuan, Taiwan. revival_chuang@yahoo.com. Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. revival_chuang@yahoo.com.Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Sec 1, Ren-Ai Road, Taipei, Taiwan. ylchenv@ntu.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29329563

Citation

Liu, Chen-Wei, et al. "PM2.5-induced Oxidative Stress Increases Intercellular Adhesion Molecule-1 Expression in Lung Epithelial Cells Through the IL-6/AKT/STAT3/NF-κB-dependent Pathway." Particle and Fibre Toxicology, vol. 15, no. 1, 2018, p. 4.
Liu CW, Lee TL, Chen YC, et al. PM2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway. Part Fibre Toxicol. 2018;15(1):4.
Liu, C. W., Lee, T. L., Chen, Y. C., Liang, C. J., Wang, S. H., Lue, J. H., Tsai, J. S., Lee, S. W., Chen, S. H., Yang, Y. F., Chuang, T. Y., & Chen, Y. L. (2018). PM2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway. Particle and Fibre Toxicology, 15(1), 4. https://doi.org/10.1186/s12989-018-0240-x
Liu CW, et al. PM2.5-induced Oxidative Stress Increases Intercellular Adhesion Molecule-1 Expression in Lung Epithelial Cells Through the IL-6/AKT/STAT3/NF-κB-dependent Pathway. Part Fibre Toxicol. 2018 01 12;15(1):4. PubMed PMID: 29329563.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PM2.5-induced oxidative stress increases intercellular adhesion molecule-1 expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-κB-dependent pathway. AU - Liu,Chen-Wei, AU - Lee,Tzu-Lin, AU - Chen,Yu-Chen, AU - Liang,Chan-Jung, AU - Wang,Shu-Huei, AU - Lue,June-Horng, AU - Tsai,Jaw-Shiun, AU - Lee,Shih-Wei, AU - Chen,Shun-Hua, AU - Yang,Yi-Fan, AU - Chuang,Tzu-Yi, AU - Chen,Yuh-Lien, Y1 - 2018/01/12/ PY - 2017/09/01/received PY - 2018/01/02/accepted PY - 2018/1/14/entrez PY - 2018/1/14/pubmed PY - 2018/10/16/medline KW - Inflammation KW - Intercellular adhesion molecule-1 (ICAM-1) KW - Interleukin-6 (IL-6) KW - Particulate matters (PMs) KW - Reactive oxygen species (ROS) SP - 4 EP - 4 JF - Particle and fibre toxicology JO - Part Fibre Toxicol VL - 15 IS - 1 N2 - BACKGROUND: Epidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo. RESULT: The cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3. Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11-7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells. In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice. Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects. CONCLUSION: These results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway. SN - 1743-8977 UR - https://www.unboundmedicine.com/medline/citation/29329563/PM2_5_induced_oxidative_stress_increases_intercellular_adhesion_molecule_1_expression_in_lung_epithelial_cells_through_the_IL_6/AKT/STAT3/NF_κB_dependent_pathway_ L2 - https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-018-0240-x DB - PRIME DP - Unbound Medicine ER -