Dexamethasone protects normal human liver cells from apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand by upregulating the expression of P-glycoproteins.
Glucocorticoids are effective for the treatment of acute-on-chronic pre-liver failure, severe chronic hepatitis B and acute liver failure; however, the mechanism underlying the effects of treatment by glucocorticoids remains to be fully elucidated. The role and detailed mechanism of how glucocorticoids prevent liver disease progression can be elucidated by investigating the apoptosis of hepatocytes following glucocorticoid treatment. P‑glycoproteins (P‑gps) also confer resistance to apoptosis induced by a diverse range of stimuli. Glucocorticoids, particularly dexamethasone (DEX), upregulate the expression of P‑gp in several tissues. In the present study, the normal human L‑02 liver cell line was used, and techniques, including immunocytochemistry, western blot analysis, flow cytometry and reverse transcription‑quantitative polymerase chain reaction analysis were used for determining the expression levels of P‑gps, and for evaluating the effect of DEX pretreatment on the expression of P‑gps. DEX (1‑10 µM) was added to the cell culture media and incubated for 24‑72 h. The results revealed that DEX upregulated the mRNA and protein levels of P‑gp in a dose‑ and time‑dependent manner. Subsequently, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) was used for the induction of apoptosis in the cells, followed by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay to assess the apoptotic stages. The results demonstrated that apoptosis in the group of cells, which were pre‑treated with DEX was significantly lower than that in the control group. Treatment with tariquidar, a P‑gp inhibitor, reduced the anti‑apoptotic effects of DEX. These results established that DEX protects normal human liver cells from TRAIL‑induced apoptosis by upregulating the expression of P-gp. These observations may be useful for elucidating the mechanism of DEX for preventing the progression of liver disease.
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Bo
B
Zhao
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Gui-Juan
GJ
Xie
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Rui-Feng
RF
Li
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Qing
Q
Chen
Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China.
Xu-Qing
XQ
Zhang
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000633:toxicity*; D015854:Up-Regulation / Q000187:drug effects*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; D003907:Dexamethasone