ABSTRACT
Acute lung injury has a range of causes, and occasionally leads to lethal respiratory failure. Despite advances in treatment, acute lung injury continues to have a high mortality rate, and thus a new therapeutic approach is needed. ST2 is an interleukin (IL)-1 receptor-related protein, and its expression is induced by various inflammatory responses. Recently, ST2 has been speculated to exert anti-inflammatory effects; therefore, we investigated the role of the ST2 in the murine model of acute lung injury. To elucidate the function of ST2 in vivo, mice that transiently overexpressed ST2 protein were prepared using the hydrodynamic gene transfer method, and lung injury was induced by intratracheal administration of bleomycin. In bleomycin-treated ST2-overexpressing mice, the increase of neutrophils in the bronchoalveolar lavage fluid (BALF) was markedly suppressed. Additionally, the levels of tumour necrosis factor-alpha and IL-6, 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.
Subject(s)
Acute Lung Injury/physiopathology , Receptors, Interleukin/physiology , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Albumins/metabolism , Analysis of Variance , Animals , Bleomycin/toxicity , Bronchoalveolar Lavage Fluid/chemistry , Enzyme-Linked Immunosorbent Assay , Gene Expression , Gene Transfer Techniques , Genetic Vectors , Interleukin-1/metabolism , Interleukin-1 Receptor-Like 1 Protein , Interleukin-33 , Interleukin-6/metabolism , Interleukins/metabolism , Male , Mice , Mice, Inbred C57BL , Plasmids , Receptors, Interleukin-1/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/metabolism , beta-Galactosidase/metabolismABSTRACT
OBJECTIVE: To study the mode of appearance of ST2 in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Immunoprecipitation and subsequent immunoblotting were performed to reveal the existence of ST2 in CSF after SAH. CSF samples from 21 patients were analyzed for ST2 using an enzyme-linked immunosorbent assay system. The ST2 levels were compared between serum and CSF after SAH. The ST2 levels in CSF were measured in six patients operated with other than SAH. RESULTS: ST2 was secreted into CSF after SAH. The concentration of ST2 was the highest in the samples of the first post-operative day and declined thereafter. The patients operated with other than SAH did not show the elevation of ST2 in CSF. CONCLUSIONS: This study revealed the presence of ST2 in CSF for the first time and suggested a possibility that ST2 is related to the inflammatory reaction in the central nervous system after SAH.
