IL-1 R-related protein ST2 suppressed the initial stage of bleomycin-induced lung injury

¹ Division of Pulmonary Medicine, Dept of Medicine, Jichi Medical University, Tochigi, Japan
² Dept of Biochemistry, Jichi Medical University
³ Dept of Basic Science, School of Veterinary Nursing and Technology, Nippon Veterinary and Life Science University
⁴ Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical University
⁵ Dept of Dermatology, Jichi Medical University

^* To whom correspondence should be addressed. E-mail: sugiyuki{at}jichi.ac.jp.

	Abstract

Acute lung injury has a range of causes, and occasionally leads to lethal respiratory failure. Despite the advances in treatment, acute lung injury continues to have a high mortality rate, and thus a new therapeutic approach is needed. ST2 is IL-1 receptor-related protein, and its expression is induced by various inflammatory responses. Recently, ST2 has been speculated to exert anti-inflammatory effects; we therefore investigated the role of the ST2 in the murine model of acute lung injury.

To elucidate the function of ST2 in vivo, we prepared mice that transiently overexpressed ST2 protein using the hydrodynamic gene transfer method, and then induced lung injury by intratracheal administration of bleomycin.

In bleomycin-treated ST2-overexpressing mice, increase of neutrophils in the bronchoalveolar lavage fluid was markedly suppressed. Additionally, the levels of TNF-, and IL-6, and as well as the concentration of albumin in BALF were reduced compared with those of controls. Furthermore, the pulmonary architecture in ST2-overexpressing mice remained almost normal, and the survival rate was significantly improved.

From these results, we concluded that ST2 has the potential to suppress the initial stage of acute lung injury, and therefore it may be a useful reagent for the treatment of acute lung injury.