The Iron Chelator and Anticancer Agent Dp44mT Relieves Allergic Inflammation in Mice With Allergic Rhinitis.

Abstract

Our previous study showed that an iron chelator and anticancer agent Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has an antiinflammatory effect in human mast cells. However, antiinflammatory effect of Dp44mT remains unclear in animal models. In this study, we assessed whether administration of Dp44mT could relieve clinical symptoms of ovalbumin (OVA)-induced allergic rhinitis (AR) mice. After administration of Dp44mT, number of rubs was significantly decreased, and levels of histamine and IgE were suppressed in serum of AR mice. Also, serum levels of interleukin (IL)-1β, thymic stromal lymphopoietin (TSLP), and tumor necrosis factor (TNF)-α increased by OVA challenge were significantly lowered by administration of Dp44mT. T helper type 1 (Th1) cytokine interferon-γ level was significantly increased by administration of Dp44mT, whereas Th2 cytokines such as IL-4, IL-5, and IL-13 were significantly reduced by administration of Dp44mT. In intranasal tissues of AR mice, levels of IL-1β, TSLP, TNF-α, and IL-6 and activities and protein levels of caspase-1 were significantly reduced by administration of Dp44mT. Interestingly, administration of Dp44mT reduced number of infiltrated eosinophils and mast cells through the inhibition of macrophage inflammatory protein-2 and intercellular adhesion molecule-1 in intranasal tissues of AR mice. In conclusion, these results indicate that Dp44mT also has potential antiinflammatory effects in vivo as well as in vitro.

• Authors: Hee-Yun Kim, Na-Ra Han, Hyung-Min Kim, Hyun-Ja Jeong
• Journal: Inflammation (Inflammation) Vol. 41 Issue 5 Pg. 1744-1754 (Oct 2018) ISSN: 1573-2576 [Electronic] United States
• PMID: 29967928 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antineoplastic Agents
• Chemokine CXCL2
• Iron Chelating Agents
• Thiosemicarbazones
• di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone
• Intercellular Adhesion Molecule-1

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Chemokine CXCL2 (antagonists & inhibitors)
• Eosinophils (drug effects)
• Inflammation (drug therapy)
• Intercellular Adhesion Molecule-1 (drug effects)
• Iron Chelating Agents (pharmacology, therapeutic use)
• Mast Cells (drug effects)
• Mice
• Rhinitis, Allergic (drug therapy, pathology)
• Thiosemicarbazones (pharmacology, therapeutic use)