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Aprepitant attenuates cutaneous mast cell migration in oxaliplatin-treated mice
1Department of Pharmacology and Pathophysiology, College of Pharmacy, Kinjo Gakuin University, 2-1723 Omori, Moriyama-ku, Nagoya, Aichi, 463-8521, Japan.
Abstract:
This study investigated whether tachykinin NK1 receptor antagonist aprepitant (APT) inhibits oxaliplatin (OXP)-induced cutaneous mast cell migration in mice. OXP-induced mast cell migration was inhibited by repeated oral administration of APT. OXP increased the expression of monocyte chemotactic protein-1 (MCP-1), stem cell factor (SCF), and interleukin-3 (IL-3), but not platelet-derived endothelial cell growth factor in the plantar skin. APT inhibited OXP-induced MCP-1, but not IL-3, expression. The expression of SCF tended to be inhibited by APT. These results suggest that APT attenuates OXP-induced cutaneous mast cell migration mainly by inhibiting the expression of MCP-1 and SCF.
Insights
Aprepitant (APT) reduces oxaliplatin (OXP)-induced skin inflammation in mice by inhibiting mast cell migration. This effect is linked to decreased expression of key inflammatory markers like monocyte chemotactic protein-1 (MCP-1) and stem cell factor (SCF).
Area of Science:
- Pharmacology
- Immunology
- Dermatology
Background:
- Oxaliplatin (OXP) is a chemotherapy drug known to cause cutaneous side effects.
- Mast cell migration in the skin plays a role in OXP-induced inflammatory responses.
- Tachykinin NK1 receptor antagonists, like aprepitant (APT), are being investigated for managing chemotherapy-induced toxicities.
Purpose of the Study:
- To investigate the effect of aprepitant (APT) on oxaliplatin (OXP)-induced cutaneous mast cell migration in a mouse model.
- To determine the impact of APT on the expression of specific chemokines and cytokines involved in mast cell recruitment.
Main Methods:
- Mice were administered oxaliplatin (OXP) to induce cutaneous mast cell migration.
- Repeated oral administration of aprepitant (APT) was used to assess its inhibitory effects.
- Expression levels of monocyte chemotactic protein-1 (MCP-1), stem cell factor (SCF), and interleukin-3 (IL-3) in plantar skin were analyzed.
Main Results:
- Oxaliplatin (OXP) induced significant mast cell migration in the skin.
- Repeated oral administration of aprepitant (APT) inhibited OXP-induced mast cell migration.
- APT significantly inhibited the OXP-induced increase in monocyte chemotactic protein-1 (MCP-1) expression.
- APT showed a trend towards inhibiting stem cell factor (SCF) expression, but not interleukin-3 (IL-3).
Conclusions:
- Aprepitant (APT) attenuates oxaliplatin (OXP)-induced cutaneous mast cell migration in mice.
- The inhibitory effect of APT is primarily mediated by the suppression of monocyte chemotactic protein-1 (MCP-1) and, to some extent, stem cell factor (SCF) expression.
- These findings suggest APT as a potential therapeutic agent for managing oxaliplatin-induced skin toxicity.
