Regulation of intrinsic apoptosis in cycloheximide-treated macrophages by the Sichuan human strain of Chinese Leishmania isolates.
Leishmania spp. are able to survive and proliferate inside mammals' mononuclear phagocytes, causing Leishmaniasis. Previous studies have noted that the regulation of apoptosis in host cells by these parasites may contribute to their ability to evade the immune system. However, current results remain unclear about whether the parasites can promote or delay the apoptotic process in host cells, because the regulatory effect of Leishmania was assumed to be strain-, species- and even infection time-dependent. The aim of this study was to investigate whether the Sichuan isolates of Chinese Leishmania (SC10H2) can alter the process of intrinsic apoptosis induced by cycloheximide in different types of macrophage cell lines and to determine in which steps of the signaling pathway the parasites were involved. Human THP-1 and mouse RAW264.7 macrophages were infected by SC10H2 promastigotes followed by cycloheximide stimulation to assess the alteration of intrinsic apoptosis in these cells. The results indicated that SC10H2 infection of human THP-1 macrophages could promote the initiation of intrinsic apoptosis, but completely opposite results were found in mouse RAW264.7 macrophages. Nevertheless, the expression of Bcl-2 and the DNA fragmentation rates were not altered by SC10H2 infection in the cell lines used in the experiments. This study suggests that SC10H2 promastigote infection is able to promote and delay the transduction of early apoptotic signals induced by cycloheximide in THP-1 and RAW264.7 macrophages, revealing that the regulation of intrinsic apoptosis in host cells by SC10H2 in vitro occurs in a host cell-dependent manner. The data from this study might play a significant role in further understanding the relationship between Leishmania and different host cells.
Department of Parasitology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Jin
J
Zeng
Department of Parasitology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Qi-Wei
QW
Chen
Department of Parasitology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Ze-Ying
ZY
Yu
Department of Parasitology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Jun-Rong
JR
Zhang
Department of Parasitology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Da-Li
DL
Chen
West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Chen
C
Song
West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Jie
J
Luo
West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Chen
C
Zhang
West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China.
Shun-Li
SL
Wang
Department of Parasitology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, PR China; Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: jpchen007@163.com.
Jian-Ping
JP
Chen
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D003513:Cycloheximide / Q000627:therapeutic use*; D006801:Humans; D007891:Leishmania / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy* / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000469:parasitology*; D051379:Mice
D000981:Antiprotozoal Agents; D003513:Cycloheximide
Apoptosis; Cycloheximide; Leishmania; RAW264.7; THP-1