Effects of IL-33/ST2 pathway in acute inflammation on tissue damage, antioxidative parameters, magnesium concentration and cytokines profile

• Published in: Experimental and molecular pathology Vol. 101; no. 1; pp. 31 - 37
• Main Authors: Stankovic, Marija S., Janjetovic, Kristina, Velimirovic, Milica, Milenkovic, Marina, Stojkovic, Tihomir, Puskas, Nela, Zaletel, Ivan, De Luka, Silvio R., Jankovic, Sasa, Stefanovic, Srdjan, Japundzic-Zigon, Nina, Petronijevic, Natasa D., Trajkovic, Vladimir, Trbovich, Alexander M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01-08-2016
• Subjects: Acute inflammation; Animals; Antioxidants; Antioxidants - metabolism; Aspartate Aminotransferases - blood; Copper - metabolism; Creatine Kinase - metabolism; Cytokines; Gene Expression Regulation; Glutathione - metabolism; Glutathione Peroxidase - metabolism; IL-33/ST2 pathway; Inflammation - blood; Inflammation - enzymology; Inflammation - genetics; Inflammation - pathology; Interleukin-1 Receptor-Like 1 Protein - genetics; Interleukin-1 Receptor-Like 1 Protein - metabolism; Interleukin-33 - genetics; Interleukin-33 - metabolism; Magnesium; Magnesium - metabolism; Male; Manganese - metabolism; Mice, Inbred BALB C; Muscles - drug effects; Muscles - metabolism; Muscles - pathology; Selenium - metabolism; Signal Transduction; Superoxide Dismutase - metabolism; Transforming Growth Factor beta - pharmacology; Mn; AST; IL; KO-I; Cytokines; TNF-alpha; Vdii; Acute inflammation; CK; SOD; Vdnf; GPx; Antioxidants; WT-I; TGF-beta; Cu; Se; KO-C; Mg; IL-33/ST2 pathway; WT-C; Magnesium; GSH
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2016.05.012

The aim of this study was to examine the role of IL-33/ST2 pathway in a pathogenesis of acute inflammation and its effects on tissue damage, antioxidative capacity, magnesium concentration and cytokine profile in acutely inflamed tissue.
Male mice were randomly divided in four groups: wild-type control group (WT-C), ST2 knockout control group (KO-C), wild-type inflammatory group (WT-I), and ST2 knockout inflammatory group (KO-I). Acute inflammation was induced in WT-I and KO-I by intramuscular injection of turpentine oil, while mice in WT-C and KO-C were treated with saline. After 12h, animals were euthanized, and blood was collected for determination of creatine kinase (CK) and aspartate transaminase (AST) activity. The treated tissue was used for histopathological analysis, determination of volume density of inflammatory infiltrate (Vdii) and necrotic fiber (Vdnf), gene expression of interleukin (IL)-33, ST2, tumor necrosis factor alpha (TNF-alpha), IL-6, IL-12p35, and transforming growth factor beta (TGF-beta), concentration of magnesium (Mg), copper (Cu), selenium (Se), manganese (Mn) and reduced glutathione (GSH), and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity.
Presence of inflammatory infiltration and necrosis in the treated tissue was histopathologically confirmed in WT-I and KO-I. Vdii was significantly higher in WT-I when compared to KO-I, whereas Vdnf did not significantly differ between WT-I and KO-I. CK and AST significantly increased in both inflammatory groups when compared to corresponding control groups. However, the values of CK and AST were significantly higher in WT-I than in KO-I. Mg in the treated tissue was significantly lower in WT-I in comparison to WT-C and KO-I, while there was no significant difference between KO-C and KO-I. There was no significant difference in Cu, Se, and Mn in the treated tissue between WT-C, KO-C, WT-I and KO-I. Gene expression of IL-33 in the treated tissue increased in both inflammatory groups when compared to the corresponding control groups, but it was significantly higher in KO-I than in WT-I. Gene expression of ST2 in the treated tissue was significantly higher in WT-I than in WT-C. Gene expression of TNF-alpha, IL-6, and IL-12p35 in the treated tissue was significantly higher in WT-I and KO-I than in the corresponding control groups, and IL-6 was significantly higher in KO-C than in WT-C. TGF-beta gene expression in the treated tissue was significantly higher in KO-I when compared to WT-I, while there was no difference between WT-C and KO-C. SOD activity decreased at the site of acute inflammation in both inflammatory groups, while the GPx activity increased. GSH in the treated tissue was significantly higher in KO-I than in KO-C or WT-I.
The results of our study have indicated, to our knowledge for the first time, that IL-33/ST2 pathway plays a role in enhancing inflammation and tissue damage at the site of acute inflammation by affecting the concentration of magnesium and GSH, important for antioxidative capacity, as well as gene expression of anti-inflammatory cytokine TGF-beta.
•IL-33/ST2 axis was important in enhancing acute inflammation and tissue damage.•IL-33/ST2 axis affected magnesium concentration in acutely inflamed tissue.•IL-33/ST2 axis affected reduced glutathione level at the site of acute inflammation.•IL-33/ST2 axis affected gene expression of TGF-beta in acutely inflamed tissue.