LukS-PV induces differentiation by activating the ERK signaling pathway and c-JUN/c-FOS in human acute myeloid leukemia cells.
LukS-PV, a component of Panton-Valentine leukocidin, is a pore-forming cytotoxin secreted by Staphylococcus aureus. Here we examined the potential effect of LukS-PV in differentiation of human leukemia cells and the underlying mechanism. We found that LukS-PV could induce differentiation of human acute myeloid leukemia (AML) cells, including AML cell lines and primary AML blasts, as determined by morphological changes, phagocytosis assay and expression of CD14 and CD11b surface antigens. In addition, LukS-PV activated the extracellular signal-regulated kinase (ERK) pathway and significantly upregulated the phosphorylation of c-JUN and c-FOS transcriptional factors in the process of differentiation. Inhibiting ERK pathway activation with U0126 (a MEK1/2 inhibitor) markedly blocked LukS-PV-induced differentiation and decreased the phosphorylation of c-JUN and c-FOS. These findings demonstrate an essential role for the ERK pathway together with c-JUN and c-FOS in the differentiation activity of LukS-PV. Taken together, our data suggest that LukS-PV could be a potential candidate as a differentiation-inducing agent for the therapeutic treatment of AML.
Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
Chunyang
C
Dai
Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
Chengfang
C
Zhang
Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
Xiaoxi
X
Sun
Department of Laboratory Medicine, Bengbu Medical College, Bengbu, China.
Qing
Q
Pan
Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
Jing
J
Peng
Anhui Provincial Laboratories of Pathogen Biology and Zoonoses, Department of Microbiology and Parasitology, Anhui Medical University, Hefei, China.
Jilong
J
Shen
Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, China. Electronic address: xiaolingma@126.com.
Xiaoling
X
Ma
D001426:Bacterial Proteins / Q000494:pharmacology*; D002070:Butadienes / Q000494:pharmacology; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007956:Leukocidins / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D013211:Staphylococcus aureus
D001426:Bacterial Proteins; D002070:Butadienes; D039481:CD11b Antigen; C509295:ITGAM protein, human; D007956:Leukocidins; D018950:Lipopolysaccharide Receptors; D009570:Nitriles; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C113580:U 0126; C108483:leukocidin S-component protein, Staphylococcus
Acute myeloid leukemia; Bacterization; Differentiation; Extracellular signal-regulated kinase pathway; Panton–Valentine leukocidin