Interleukin-33 induces interleukin-17F in bronchial epithelial cells

J. Fujita, M. Kawaguchi, F. Kokubu, G. Ohara, K. Ota, S. K. Huang, Y. Morishima, Y. Ishii, H. Satoh, T. Sakamoto, N. Hizawa

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. Methods Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. Results IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. Conclusions IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.

Original languageEnglish
Pages (from-to)744-750
Number of pages7
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume67
Issue number6
DOIs
Publication statusPublished - Jun 1 2012
Externally publishedYes

Fingerprint

Interleukin-17
Epithelial Cells
Heat-Shock Proteins
Mitogens
Asthma
Phosphotransferases
Mitogen-Activated Protein Kinase Kinases
Small Interfering RNA
Interleukin-33
Transfection
Real-Time Polymerase Chain Reaction
Western Blotting
Enzyme-Linked Immunosorbent Assay
Phosphorylation
Inflammation
Gene Expression

Keywords

  • bronchial epithelial cell
  • IL-17F
  • IL-33

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Interleukin-33 induces interleukin-17F in bronchial epithelial cells. / Fujita, J.; Kawaguchi, M.; Kokubu, F.; Ohara, G.; Ota, K.; Huang, S. K.; Morishima, Y.; Ishii, Y.; Satoh, H.; Sakamoto, T.; Hizawa, N.

In: Allergy: European Journal of Allergy and Clinical Immunology, Vol. 67, No. 6, 01.06.2012, p. 744-750.

Research output: Contribution to journalArticle

Fujita, J, Kawaguchi, M, Kokubu, F, Ohara, G, Ota, K, Huang, SK, Morishima, Y, Ishii, Y, Satoh, H, Sakamoto, T & Hizawa, N 2012, 'Interleukin-33 induces interleukin-17F in bronchial epithelial cells', Allergy: European Journal of Allergy and Clinical Immunology, vol. 67, no. 6, pp. 744-750. https://doi.org/10.1111/j.1398-9995.2012.02825.x
Fujita, J. ; Kawaguchi, M. ; Kokubu, F. ; Ohara, G. ; Ota, K. ; Huang, S. K. ; Morishima, Y. ; Ishii, Y. ; Satoh, H. ; Sakamoto, T. ; Hizawa, N. / Interleukin-33 induces interleukin-17F in bronchial epithelial cells. In: Allergy: European Journal of Allergy and Clinical Immunology. 2012 ; Vol. 67, No. 6. pp. 744-750.
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abstract = "Background IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. Methods Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. Results IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. Conclusions IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.",
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T1 - Interleukin-33 induces interleukin-17F in bronchial epithelial cells

AU - Fujita, J.

AU - Kawaguchi, M.

AU - Kokubu, F.

AU - Ohara, G.

AU - Ota, K.

AU - Huang, S. K.

AU - Morishima, Y.

AU - Ishii, Y.

AU - Satoh, H.

AU - Sakamoto, T.

AU - Hizawa, N.

PY - 2012/6/1

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N2 - Background IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. Methods Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. Results IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. Conclusions IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.

AB - Background IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. Methods Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. Results IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. Conclusions IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.

KW - bronchial epithelial cell

KW - IL-17F

KW - IL-33

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