| RRC ID |
72419
|
| 著者 |
Kawase A, Takashima O, Tanaka S, Shimada H, Iwaki M.
|
| タイトル |
Diclofenac-Induced Cytotoxicity in Direct and Indirect Co-Culture of HepG2 Cells with Differentiated THP-1 Cells.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac (DIC) frequently induce drug-induced liver injury (DILI). It is unclear whether macrophages such as M1 and M2 participate in NSAID-associated DILI; elucidating this relationship could lead to a better understanding of the detailed mechanism of DILI. We co-cultured human hepatoma HepG2 cells with M1 or M2 derived from human monocytic leukemia THP-1 cells to examine the roles of M1 and M2 in DIC-induced cytotoxicity. DIC was added to the direct or indirect co-cultures of HepG2 cells with M1 or M2 (HepG2/M1 or HepG2/M2, respectively) at cell ratios of (1:0, 1:0.1, 1:0.4, and 1:1). In both direct and indirect HepG2/M2 co-cultures (1:0.4), there was lower lactate dehydrogenase release compared with HepG2/M1 co-cultures. Other NSAIDs as well as DIC showed similar protective effects of DIC-induced cytotoxicity. There were only slight differences in mRNA levels of apoptosis- and endoplasmic reticulum stress-associated factors between M1 and M2 after DIC treatment, suggesting that other factors determined the protective effects of M2 on DIC-induced cytotoxicity. Levels of high mobility group box 1 (HMGB1) in the medium and the mRNA expression levels of HMGB1 receptors were different between M1 and M2 after DIC treatment. Increased HMGB1 concentrations and expression of toll-like receptor 2 mRNA in M1 were observed compared with M2 after DIC treatment. In conclusion, these results suggested that the HMGB1/TLR2 signaling axis can be suppressed in M2 but not M1, leading to the different roles of M1 and M2 in NSAID-induced cytotoxicity.
|
| 巻・号 |
23(15)
|
| 公開日 |
2022-8-4
|
| DOI |
10.3390/ijms23158660
|
| PII |
ijms23158660
|
| PMID |
35955793
|
| PMC |
PMC9368861
|
| MeSH |
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Chemical and Drug Induced Liver Injury* / etiology
Coculture Techniques
Dacarbazine
Diclofenac / metabolism
Diclofenac / toxicity
HMGB1 Protein* / genetics
Hep G2 Cells
Humans
RNA, Messenger
THP-1 Cells
|
| IF |
4.556
|
| リソース情報 |
| ヒト・動物細胞 |
Hep G2(RCB1886)
THP-1(RCB1189) |
