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Activation of cytokine production, tumoricidal properties, and tyrosine phosphorylation of MAPKs in human monocytes by a new synthetic lipopeptide, JBT3002.
- Source :
-
Journal of leukocyte biology [J Leukoc Biol] 1998 Jun; Vol. 63 (6), pp. 766-74. - Publication Year :
- 1998
-
Abstract
- 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 alpha, interleukin-1beta, and interleukin-6 in a dose-dependent manner with similar kinetics. Treatment of monocytes with interferon-gamma 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.
- Subjects :
- Cytotoxicity, Immunologic drug effects
Humans
Leukocytes, Mononuclear immunology
Lipopeptides
Lipopolysaccharide Receptors metabolism
Lipopolysaccharide Receptors physiology
Lipopolysaccharides pharmacology
Liposomes
Lymphocyte Activation drug effects
Phosphorylation drug effects
RNA, Messenger metabolism
Signal Transduction drug effects
Adjuvants, Immunologic pharmacology
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Cytokines biosynthesis
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear metabolism
Lipoproteins pharmacology
Tyrosine metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0741-5400
- Volume :
- 63
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of leukocyte biology
- Publication Type :
- Academic Journal
- Accession number :
- 9620671
- Full Text :
- https://doi.org/10.1002/jlb.63.6.766