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IL-1β Upregulates IL-8 Production in Human Müller Cells Through Activation of the p38 MAPK and ERK1/2 Signaling Pathways

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Abstract

Diabetic retinopathy shares some similarity with chronic inflammation and Müller cells dysfunction may play an important role in its initiation and progression since these cells are thought to be a major source of inflammatory factors. The goal of this study was to examine the effect of cytokines on human retinal Müller cells and to understand the underlying signal transduction pathways regulating interleukin-8 (IL-8) expression. In this study, human MIO-M1 cells were treated with interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-8, vascular endothelial growth factor (VEGF), interferon-gamma (IFN-γ), glucose, or mannitol, followed by examination of their IL-8 protein and mRNA levels by Western blotting and PCR, respectively. After treatment with IL-1β, the levels of phosphorylated p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) were measured. IL-8 was also measured by Western blotting and ELISA following Müller cell culture with IL-1β and specific inhibitors of the p38 MAPK, ERK1/2, JNK, or JAK2 pathways. The results showed that IL-1β was a potent inducer of IL-8 expression in MIO-M1 cells, although a relatively small increase was induced by TNF-α. IL-6, IL-8, VEGF, and IFN-γ did not modify IL-8 expression. Increase of IL-8 expression was accompanied by a significant increased phosphorylation of p38 MAPK, ERK, and JNK, but not of JAK2 and STAT3. Furthermore, inhibitors of p38 MAPK and MEK1/2, but not for JNK and JAK2, significantly inhibited IL-8 expression. In conclusion, IL-1β potently stimulates IL-8 expression in Müller cells mainly through the p38 MAPK and ERK1/2 pathways.

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ACKNOWLEDGMENTS

The author thanks Weihua Tong for reference input, and thanks Guodong Lian, Chang Shu, and Zhiqing Wang for technical support. No conflicts of interest relevant to this article were reported.

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Authors and Affiliations

  1. Department of Ophthalmology, The First Hospital, Jilin University, Changchun, Jilin, 130021, China

    Xiufen Liu, Wei Yang, Yabin Sun & E Song

  2. Department of Pathology, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Fei Ye & David Y. Zhang

  3. Department of Medicine, Immunology Institute, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Huabao Xiong & Liang Peng

  4. Tissue Culture Center, New York Eye and Ear Infirmary, New York, NY, 10029, USA

    Danning Hu

  5. Division of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, Bath Street, London, EC1V 9EL, UK

    G. Astrid Limb

  6. Department of neurosurgery, The People’s Hospital of Jilin Province, Changchun, Jilin, 130021, China

    Tian Xie

  7. Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Mingming Zhou

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  1. Xiufen Liu
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Liu, X., Ye, F., Xiong, H. et al. IL-1β Upregulates IL-8 Production in Human Müller Cells Through Activation of the p38 MAPK and ERK1/2 Signaling Pathways. Inflammation 37, 1486–1495 (2014). https://doi.org/10.1007/s10753-014-9874-5

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