Mechanism of Periostin Production in Human Bronchial Smooth Muscle Cells.

Abstract

BACKGROUND:

Asthma is a chronic airway inflammatory disease characterized by airway remodeling, in which the bronchial smooth muscle (BSM) cells play an important role. Periostin, a biomarker that reflects Th2-driven inflammatory diseases such as asthma, may play an important role in the asthmatic airway. Although periostin is mainly produced in airway epithelial cells and fibroblasts after interleukin (IL)-13 stimulation, whether BSM cells produce periostin remains unclear. Therefore, we investigated periostin production in BSM cells and the mechanisms involved.

METHODS:

Human BSM cells were cultured, and the effect of IL-13 stimulation on periostin production was evaluated using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). We evaluated the phosphorylation of signal transducer and activator of transcription factor 6 (STAT6), extracellular signal-regulated kinase (ERK)1/2, and Akt after IL-13 stimulation. Furthermore, using ELISA, we evaluated the influence of several phosphorylation inhibitors on periostin production.

RESULTS:

Periostin mRNA expression increased in a dose- and time-dependent manner after IL-13 stimulation; periostin production was induced 24 and 48 h after stimulation. IL-13 stimulation induced the phosphorylation of STAT6, ERK1/2, and Akt. IL-13-induced periostin production was attenuated by inhibiting STAT6 phosphorylation and strongly suppressed by inhibiting mitogen-activated protein kinase kinase 1/2 phosphorylation or phosphatidylinositol 3-kinase (PI3K) phosphorylation.

CONCLUSIONS:

BSM cells produced periostin after IL-13 stimulation, via the JAK/STAT6, ERK1/2, and PI3K/Akt pathways. Understanding the mechanism of periostin production in BSM cells may help to clarify asthma pathogenesis.

• Authors: Kosuke Makita, Yu Mikami, Hirotaka Matsuzaki, Naoya Miyashita, Hideyuki Takeshima, Satoshi Noguchi, Masafumi Horie, Hirokazu Urushiyama, Motoyasu Iikura, Masayuki Hojo, Takahide Nagase, Yasuhiro Yamauchi
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 175 Issue 1-2 Pg. 26-35 ( 2018) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 29342461 (Publication Type: Journal Article)
• Copyright: © 2018 S. Karger AG, Basel.

Chemical References

• Cell Adhesion Molecules
• Interleukin-13
• POSTN protein, human
• STAT6 Transcription Factor
• STAT6 protein, human
• Phosphatidylinositol 3-Kinases
• Oncogene Protein v-akt
• Mitogen-Activated Protein Kinase 3

Topics

• Airway Remodeling
• Asthma (immunology)
• Bronchi (immunology)
• Cell Adhesion Molecules (genetics, metabolism)
• Cells, Cultured
• Humans
• Interleukin-13 (immunology)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Myocytes, Smooth Muscle (physiology)
• Oncogene Protein v-akt (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• STAT6 Transcription Factor (metabolism)
• Signal Transduction
• Up-Regulation