TY - JOUR
T1 - Activation of cytokine production, tumoricidal properties, and tyrosine phosphorylation of MAPKs in human monocytes by a new synthetic lipopeptide, JBT3002
AU - Dong, Zhongyun
AU - Killion, Jerald J.
AU - Kumar, Rakesh
AU - Eue, Inès
AU - Yang, Xiulan
AU - Lu, Weixin
AU - Su, Bing
AU - Fidler, Isaiah J.
PY - 1998/6
Y1 - 1998/6
N2 - We investigated the expression of cytokine genes and tumoricidal properties in human blood monocytes in response to a new synthetic immunomodulating lipopeptide, JBT3002. Incubation of peripheral blood monocytes with free-form JBT3002 or JBT3002 encapsulated in multilamellar phospholipid vesicles (liposomes, MLV-JBT3002) induced tumoricidal properties in a dose-dependent manner. Both MLV-JBT3002 and free-form JBT3002 induced production of tumor necrosis factor α, interleukin-1β, and interleukin-6 in a dose-dependent manner with similar kinetics. Treatment of monocytes with interferon-γ did not significantly alter the expression of cytokine genes but increased the expression of cytokines induced by MLV-JBT3002 and free- form JBT3002. In contrast to monocyte activation by lipopolysaccharide (LPS), activation by JBT3002 was independent of serum and was not inhibited by CD14- neutralizing antibody. Incubation of monocytes with JBT3002 induced a rapid increase in tyrosine phosphorylation of proteins with apparent molecular masses of 42 and 38 kDa, a migration band shift of c-Jun NH2-terminal kinase 1 (JNK1), and activation of extracellular signaling regulated kinases. Consistent with its effect on cytokine expression, stimulation of these intracellular signaling pathways by JBT3002 was not inhibited in serum-free conditions. Collectively, the data indicate that the synthetic lipopeptide JBT3002 is a potent monocyte activator that modulates monocyte function by mechanisms similar to LPS but by a distinct receptor.
AB - We investigated the expression of cytokine genes and tumoricidal properties in human blood monocytes in response to a new synthetic immunomodulating lipopeptide, JBT3002. Incubation of peripheral blood monocytes with free-form JBT3002 or JBT3002 encapsulated in multilamellar phospholipid vesicles (liposomes, MLV-JBT3002) induced tumoricidal properties in a dose-dependent manner. Both MLV-JBT3002 and free-form JBT3002 induced production of tumor necrosis factor α, interleukin-1β, and interleukin-6 in a dose-dependent manner with similar kinetics. Treatment of monocytes with interferon-γ did not significantly alter the expression of cytokine genes but increased the expression of cytokines induced by MLV-JBT3002 and free- form JBT3002. In contrast to monocyte activation by lipopolysaccharide (LPS), activation by JBT3002 was independent of serum and was not inhibited by CD14- neutralizing antibody. Incubation of monocytes with JBT3002 induced a rapid increase in tyrosine phosphorylation of proteins with apparent molecular masses of 42 and 38 kDa, a migration band shift of c-Jun NH2-terminal kinase 1 (JNK1), and activation of extracellular signaling regulated kinases. Consistent with its effect on cytokine expression, stimulation of these intracellular signaling pathways by JBT3002 was not inhibited in serum-free conditions. Collectively, the data indicate that the synthetic lipopeptide JBT3002 is a potent monocyte activator that modulates monocyte function by mechanisms similar to LPS but by a distinct receptor.
KW - CD14
KW - Lipopeptide JBT3002
KW - Lipopolysaccharide
KW - Monocytes/macrophages
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U2 - 10.1002/jlb.63.6.766
DO - 10.1002/jlb.63.6.766
M3 - Article
C2 - 9620671
AN - SCOPUS:0031748142
SN - 0741-5400
VL - 63
SP - 766
EP - 774
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -