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Leukemia inhibitory factor induces interleukin-8 and monocyte chemotactic and activating factor in human monocytes:
T Musso1, R Badolato, D L Longo
1PRI/DynCorp, NCI-FCRDC, Biological Carcinogenesis and Development Program, MD 21702-1201, USA.
Insights
Leukemia inhibitory factor (LIF) recruits leukocytes to injury sites by increasing interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF) in monocytes. Interferon-gamma (IFN-gamma) differentially regulates this process.
Area of Science:
- Immunology
- Cell Biology
- Cytokine Signaling
Background:
- Leukemia inhibitory factor (LIF) is a cytokine implicated in injury responses.
- Monocytes are key players in inflammation and immune cell recruitment.
- Understanding cytokine-mediated monocyte activation is crucial for inflammatory disease research.
Purpose of the Study:
- To investigate the effect of LIF on human monocyte function.
- To determine if LIF influences the production of chemotactic factors by monocytes.
- To elucidate the role of LIF in leukocyte recruitment.
Main Methods:
- Human monocytes were treated with LIF (50 ng/mL).
- Supernatant chemotactic activity was assessed using neutrophil and monocyte migration assays.
- Neutralizing antibodies against IL-8 and MCAF were used.
- Northern blot analysis was performed to detect IL-8 and MCAF mRNA expression.
- The impact of Interferon-gamma (IFN-gamma) on LIF-induced gene expression was evaluated.
Main Results:
- LIF-treated monocyte supernatants exhibited chemotactic activity for neutrophils and monocytes.
- This chemotactic activity was neutralized by anti-IL-8 and anti-MCAF antibodies.
- LIF induced the expression of IL-8 and MCAF mRNA in monocytes.
- IL-8 and MCAF mRNA levels peaked at 6 and 18 hours, respectively.
- IFN-gamma inhibited LIF-induced IL-8 expression but enhanced MCAF expression.
Conclusions:
- LIF plays a significant role in leukocyte recruitment to injury sites by inducing IL-8 and MCAF production in monocytes.
- IFN-gamma differentially modulates LIF-mediated leukocyte recruitment by affecting IL-8 and MCAF expression.
- These findings highlight a complex interplay between cytokines in regulating inflammatory cell migration.
Abstract:
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.
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