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Activation of cytokine production, tumoricidal properties, and tyrosine phosphorylation of MAPKs in human monocytes by a new synthetic lipopeptide, JBT3002
Author(s) -
Dong Zhongyun,
Killion Jerald J.,
Kumar Rakesh,
Eue Ines,
Yang Xiulan,
Lu Weixin,
Su Bing,
Fidler Isaiah J.
Publication year - 1998
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.63.6.766
Subject(s) - lipopeptide , biology , phosphorylation , tyrosine phosphorylation , cytokine , monocyte , tyrosine , protein tyrosine kinases , microbiology and biotechnology , tyrosine kinase , immunology , cancer research , biochemistry , signal transduction , bacteria , genetics
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 NH 2 ‐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. J. Leukoc. Biol . 63: 766–774; 1998.