Effect of S100A8 and S100A9 on expressions of cytokine and skin barrier protein in human keratinocytes

Kim,Mun  Jeong; Im,Mi  Ae; Lee,Ji‑Sook; Mun,Ji  Young; Kim,Da  Hye; Gu,Ayoung; Kim,In  Sik

doi:10.3892/mmr.2019.10454

Effect of S100A8 and S100A9 on expressions of cytokine and skin barrier protein in human keratinocytes

Authors:
- Mun Jeong Kim
- Mi Ae Im
- Ji‑Sook Lee
- Ji Young Mun
- Da Hye Kim
- Ayoung Gu
- In Sik Kim
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Affiliations: Department of Senior Healthcare, BK21 Plus Program, Graduate School, Eulji University, Daejeon 34824, Republic of Korea, Department of Biomedical Laboratory Science, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea, Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, Jeollabuk 54538, Republic of Korea
Published online on: July 1, 2019 https://doi.org/10.3892/mmr.2019.10454
Pages: 2476-2483

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Abstract

Atopic dermatitis (AD) is an inflammatory skin disorder caused by immunological dysregulation and genetic factors. Whether the expression levels of cytokine and skin barrier protein were altered by S100 calcium binding protein A8 (S100A8) and S100A9 in human keratinocytic HaCaT cells was examined in the present study. Alterations of cytokine expression were examined by ELISA following treatment with S100A8/9 and various signal protein‑specific inhibitors. Activation of the mitogen activated protein kinase (MAPK) pathway and nuclear factor (NF)‑κB was evaluated by using western blotting and an NF‑κB activity test, respectively. The expression levels of interleukin (IL)‑6, IL‑8 and monocyte chemoattractant protein‑1 increased following treatment with S100A8 and S100A9, and the increase was significantly blocked by specific signaling pathway inhibitors, including toll‑like receptor 4 inhibitor (TLR4i), rottlerin, PD98059, SB203580 and BAY‑11‑7085. Extracellular signal‑regulated kinase (ERK) and p38 MAPK pathways were activated in a time‑dependent manner following treatment with S100A8 and S100A9. Phosphorylation of ERK and p38 MAPK were blocked by TLR4i and rottlerin. S100A8 and S100A9 induced translocation of NF‑κB in a time‑dependent manner, and the activation of NF‑κB was inhibited by TLR4i, rottlerin, PD98059 and SB203580. In addition, S100A8 and S100A9 decreased the expression of skin barrier proteins, filaggrin and loricrin. These results may help to elucidate the pathogenic mechanisms of AD and develop clinical strategies for controlling AD.

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