Interleukin-25 induces pulmonary arterial remodeling via natural killer T cell-dependent mechanisms.

Abstract

BACKGROUND:

Recent studies have shown that prolonged Th2-type immune inflammation in the lung induces pulmonary arterial remodeling, in part through the induction of resistin-like molecule α (RELMα) expression. However, the role of interleukin-25 (IL-25; which promotes this inflammation) in the development of the pulmonary arterial remodeling remains unknown.

METHODS:

Ovalbumin (OVA)-sensitized C57BL/6 mice were challenged with OVA inhalation 3 times a week for 3 weeks. The effects of neutralizing anti-IL-25 antibody on OVA-induced pulmonary arterial remodeling and RELMα expression in the lung were examined. The pulmonary arterial remodeling and RELMα expression in the lung were examined in lung-specific IL-25 transgenic mice (CC10 IL-25 mice) and CC10 IL-25 mice in a natural killer T (NKT) cell-deficient background (CC10 IL-25 NKT(-/-) mice).

RESULTS:

Repeated OVA inhalation induced pulmonary arterial wall thickening and the expression of IL-25 and RELMα mRNA in the lung in OVA-sensitized mice. Injection of neutralizing anti-IL-25 antibody inhibited OVA-induced pulmonary arterial wall thickening and RELMα expression in the lung. CC10 IL-25 mice, but not CC10 IL-25 NKT(-/-) mice, spontaneously developed pulmonary arterial wall thickening and RELMα expression in the lung at 6 months of age.

CONCLUSIONS:

Prolonged expression of IL-25 in the lung induces pulmonary arterial wall thickening by NKT cell-dependent mechanisms.

• Authors: Saki Kawashima, Koichi Hirose, Kentaro Takahashi, Tomohiro Tamachi, Kei Ikeda, Koji Tokoyoda, Toshinori Nakayama, Hiroshi Nakajima
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 161 Suppl 2 Pg. 118-24 ( 2013) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 23711862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Antigens
• Interleukin-17
• Scgb1a1 protein, mouse
• Ovalbumin
• Uteroglobin

Topics

• Animals
• Antigens (immunology)
• Female
• Interleukin-17 (genetics, immunology)
• Mice
• Mice, Transgenic
• Natural Killer T-Cells (immunology, metabolism)
• Ovalbumin (immunology)
• Pulmonary Artery (immunology, metabolism, pathology)
• Uteroglobin (genetics, immunology)