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Secretoglobin 3A2 Attenuates Lipopolysaccharide-Induced Inflammation Through Inhibition of ERK and JNK Pathways in Bronchial Epithelial Cells

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Abstract

Secretoglobin (SCGB) 3A2, previously known as uteroglobin-related protein 1, is a secreted protein highly expressed in the epithelial cells of the airways. It has been demonstrated that SCGB3A2 is involved in allergic airway inflammation such as bronchial asthma. However, the role of SCGB3A2 in lipopolysaccharide (LPS)-induced airway inflammation has yet to be reported. The goal of this study was therefore to clarify the role of SCGB3A2 in LPS-induced airway inflammation. We stimulated BEAS-2B, human bronchial epithelial cells, with LPS and analyzed messenger RNA (mRNA) expression of tumor necrosis factor (TNF)-α and CXCL8 with or without pre-incubation of SCGB3A2. The mRNA expression of TNF-α and CXCL8 was clearly upregulated 3 h after LPS stimulation, and pre-incubation of SCGB3A2 significantly inhibited the upregulation of the mRNA expression. The pre-incubation of SCGB3A2 also inhibited LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase in BEAS-2B cells. Furthermore, PD98059, a specific inhibitor for ERK, as well as SP600125, a specific inhibitor for JNK, inhibited LPS-induced mRNA upregulation of inflammatory mediators. These results demonstrate the novel biological activity of SCGB3A2, which is that it attenuates LPS-induced inflammation in bronchial epithelial cells through inhibition of ERK and JNK activation.

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Acknowledgments

This study was partly supported by a grant to the Diffuse Lung Diseases Research Group from the Ministry of Health, Labour and Welfare, Japan.

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Authors and Affiliations

  1. Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan

    Xintao Wang, Yoshinori Tanino, Suguru Sato, Takefumi Nikaido, Kenichi Misa, Naoko Fukuhara, Atsuro Fukuhara, Junpei Saito, Hiroshi Yokouchi, Takashi Ishida & Mitsuru Munakata

  2. Department of Immunology, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima City, Fukushima, 960-1295, Japan

    Teizo Fujita

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  1. Xintao Wang
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  2. Yoshinori Tanino
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  3. Suguru Sato
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  4. Takefumi Nikaido
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  5. Kenichi Misa
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  6. Naoko Fukuhara
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  7. Atsuro Fukuhara
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  8. Junpei Saito
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  9. Hiroshi Yokouchi
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  10. Takashi Ishida
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  11. Teizo Fujita
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  12. Mitsuru Munakata
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Correspondence to Yoshinori Tanino.

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Wang, X., Tanino, Y., Sato, S. et al. Secretoglobin 3A2 Attenuates Lipopolysaccharide-Induced Inflammation Through Inhibition of ERK and JNK Pathways in Bronchial Epithelial Cells. Inflammation 38, 828–834 (2015). https://doi.org/10.1007/s10753-014-9992-0

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  • DOI: https://doi.org/10.1007/s10753-014-9992-0

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