Thromboxane A<sub>2</sub> receptor signaling in macrophages promotes liver repair after acetaminophen-induced liver injury
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- Tanabe Mina
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Ito Yoshiya
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Osada Mayuko
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Yamazaki Takuya
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Kuroda Yu
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Kamata Mariko
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Hosono Kanako
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Hatanaka Kou
- Dept. Pharm., Sch. Med., Kitasato Univ.
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- Majima Masataka
- Fac. Health&Med. Sci., Kanagawa Inst. Tech.
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- Amano Hideki
- Dept. Pharm., Sch. Med., Kitasato Univ.
Bibliographic Information
- Other Title
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- マクロファージにおけるトロンボキサンA<sub>2</sub>受容体シグナルはアセトアミノフェン誘導肝障害後の肝修復を促進する
Abstract
<p>Objective: Acetaminophen (APAP) overdose causes severe acute liver failure. Impaired liver repair and regeneration after APAP hepatotoxicity leads to failed recovery and mortality. Accumulating evidence indicates that macrophages play a critical role in liver repair after APAP-induced liver injury; however, underlying mechanisms of involvement of macrophages remain unknown. Here, we examined the role of endogenous thromboxane A2 (TXA2) in macrophages in liver repair after APAP-induced liver injury.</p><p> </p><p>Methods and Results: APAP (300 mg/kg, ip) was administered to macrophage-specific thromboxane prostanoid receptor (TP) deficient mice (mTPKO) and control mice (Cont). Compared with Cont, mTPKO exhibited severe liver injury as indicated by increased levels of ALT, necrotic area, and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and decreased expression of PCNA, a marker of hepatocyte proliferation at 48 h after APAP treatment. CD68-positive macrophages less accumulated in the livers from mTPKO, accompanied by reduced expressions of chemokines. Flow cytometry analysis revealed that the numbers of M1 macrophages in mTPKO were higher than control, while the numbers of M2 macrophages in mTPKO were lower than control. In cultured bone marrow-derived macrophages from mTPKO, M1-related gene expressions were increased and M2-related gene expressions were decreased.</p><p>Conclusions: TP receptor signaling in macrophages promoted liver repair after APAP-induced liver injury by accumulating M2 macrophages in the livers.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 97 (0), 2-B-YIA5-2-, 2023
Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390861692692493696
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
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- Abstract License Flag
- Disallowed