Leukemia inhibitory factor induces interleukin-8 and monocyte chemotactic and activating factor in human monocytes: differential regulation by interferon-gamma.
Leukemia inhibitory factor (LIF) is a cytokine released at the site of injuries where there is a recruitment of monocytes and polymorphonuclear cells. We analyzed the effect of LIF on human monocytes, which are a major source of chemotactic factors. We showed that supernatants of monocytes treated with LIF (50 ng/mL) for 18 hours had chemotactic activity for neutrophils and monocytes that was neutralized by anti-interleukin-8 (anti-IL-8) and anti-monocyte chemotactic and activating factor (anti-MCAF) neutralizing antibodies. Northern blot analysis showed induction of IL-8 and MCAF RNA in monocytes treated with LIF. Both IL-8 and MCAF mRNA were induced within 3 hours of stimulation. IL-8 and MCAF mRNAs expression peaked at 6 hours and 18 hours, respectively. Interferon-gamma (IFN-gamma), a potent monocyte activator, inhibited IL-8 induction by LIF. On the contrary, IFN-gamma by itself induced MCAF and did not affect the LIF-induced MCAF. These results indicate that LIF released at the site of injury by inducing IL-8 and MCAF can play an important role in recruiting leukocytes and that IFN-gamma can differentially regulate this recruitment.
Musso
T
T
PRI/DynCorp, NCI-FCRDC, Biological Carcinogenesis and Development Program, MD 21702-1201, USA.
Badolato
R
R
Longo
D L
DL
Gusella
G L
GL
Varesio
L
L
D015152:Blotting, Northern; D002450:Cell Communication; D002478:Cells, Cultured; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D003470:Culture Media; D016207:Cytokines / Q000096:biosynthesis*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6; D016209:Interleukin-8 / Q000096:biosynthesis*; D007700:Kinetics; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018932:Chemokine CCL2; D002630:Chemotactic Factors; D003470:Culture Media; D016207:Cytokines; D006131:Growth Inhibitors; D015850:Interleukin-6; D016209:Interleukin-8; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma