Int J Med Sci 2020; 17(4):498-509. doi:10.7150/ijms.37833

Research Paper

Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma

Da Hye Kim1*, Ayoung Gu1*, Ji-Sook Lee2, Eun Ju Yang3, Ayesha Kashif1, Min Hwa Hong1, Geunyeong Kim1, Beom Seok Park1,4, Soo Jin Lee5✉, In Sik Kim1,6✉

1. Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University, Daejeon 34824
2. Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, 54538
3. Department of Clinical Laboratory Science, Daegu Haany University, Gyeongsan, 38610
4. Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Seongnam 13135
5. Department of Pediatrics, School of Medicine, Eulji University, Daejeon, 301-746
6. Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea
*These authors contributed equally to this work

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Citation:
Kim DH, Gu A, Lee JS, Yang EJ, Kashif A, Hong MH, Kim G, Park BS, Lee SJ, Kim IS. Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma. Int J Med Sci 2020; 17(4):498-509. doi:10.7150/ijms.37833. Available from http://www.medsci.org/v17p0498.htm

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Abstract

S100A8 and S100A9 are important proteins in the pathogenesis of allergy. Asthma is an allergic lung disease, characterized by bronchial inflammation due to leukocytes, bronchoconstriction, and allergen-specific IgE. In this study, we examined the role of S100A8 and S100A9 in the interaction of cytokine release from bronchial epithelial cells, with constitutive apoptosis of neutrophils. S100A8 and S100A9 induce increased secretion of neutrophil survival cytokines such as MCP-1, IL-6 and IL-8. This secretion is suppressed by TLR4 inhibitor), LY294002, AKT inhibitor, PD98059, SB202190, SP600125, and BAY-11-7085. S100A8 and S100A9 also induce the phosphorylation of AKT, ERK, p38 MAPK and JNK, and activation of NF-κB, which were blocked after exposure to TLR4i, LY294002, AKTi, PD98059, SB202190 or SP600125. Furthermore, supernatants collected from bronchial epithelial cells after S100A8 and S100A9 stimulation suppressed the apoptosis of normal and asthmatic neutrophils. These inhibitory mechanisms are involved in suppression of caspase 9 and caspase 3 activation, and BAX expression. The degradation of MCL-1 and BCL-2 was also blocked by S100A8 and S100A9 stimulation. Essentially, neutrophil apoptosis was blocked by co-culture of normal and asthmatic neutrophils with BEAS-2B cells in the presence of S100A8 and S100A9. These findings will enable elucidation of asthma pathogenesis.

Keywords: S100A8, S00A9, Asthma, Neutrophil apoptosis, Cytokine