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Effects of the NF-κB Pathway Agonist IL-1β on Non-Small Cell Lung Cancer Cell Lines
Dong Liu1, Xiao-Qing Liu2, Rosemarie Kiefl2
1Division of Respiratory Medicine and Thoracic Oncology, Medizinische Klinik V, Ludwig-Maximilians University (LMU) Munich, Germany medicaldong@163.com.
Objective:
Canakinumab is an interleukin (IL)-1β inhibitory antibody. Recently, a large trial of canakinumab in cardiac patients described lower lung cancer incidence in patients treated with canakinumab compared to controls. This finding is the basis for ongoing clinical trials of canakinumab in lung cancer. To address the underlying mechanism, we established lung cancer co-cultures to investigate the interactions between lung cancer cells and immunocyte macrophages as related to the expression of IL-1β and the effect of IL-1β on the NF-κB pathway on lung cancer cells.
Methods:
Lung cancer cell lines H838 and H1975 and macrophages were mono-cultured separately as control groups. Lung cancer cell lines and macrophages were co-cultured respectively in a ratio of 5:1 under the conditions of 37°C in a humidified atmosphere of 5% CO2 for seven days. Cell culture supernatants were collected at predetermined time points, and cell morphology was observed and photographed by microscopy. IL-1β was detected by ELISA. H838 and H1975 cells were treated with PBS or IL-1β for 24 hours. Cells were harvested and lysed, then analyzed in a proteome profiler array.
Results:
Cells in co-cultures initially grew well. IL-1β was almost undetectable in lung cancer cell lines and macrophage monoculture groups but was highly expressed in co-cultures after 24h and declined at the 7th day. In the H838 and H1975 co-culture group, the lung cancer cells occupied a great majority. IL-1β activates the NF-κB pathway on H838 and H1975 cells.
Conclusion:
Our data showed that in a lung cancer co-culture incorporating lung cancer cells and macrophages lead to a higher expression of IL-1β than monoculture. It is possible that such dynamic changes in IL-1β expression may also occur in vivo in response to changes in the tumor microenvironment and interactions with immune cell populations. These interactions are likely important components to be considered when studying and modeling the expression of IL-1β as a potential therapeutic target in lung cancer.
Insights
Lung cancer cells and macrophages co-cultured showed increased interleukin-1 beta (IL-1β) expression. This suggests IL-1β interactions within the tumor microenvironment are crucial for lung cancer progression and potential therapeutic targeting.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Interleukin-1 beta (IL-1β) is implicated in cancer biology.
- Canakinumab, an IL-1β inhibitor, showed reduced lung cancer incidence in a cardiac trial, prompting further investigation.
- Understanding IL-1β's role in lung cancer requires examining its interaction with immune cells.
Purpose of the Study:
- To investigate the interaction between lung cancer cells and macrophages.
- To determine the expression of IL-1β in co-cultured lung cancer and macrophage models.
- To assess the effect of IL-1β on the NF-κB pathway in lung cancer cells.
Main Methods:
- Lung cancer cell lines (H838, H1975) and macrophages were co-cultured at a 5:1 ratio for seven days.
- Interleukin-1 beta (IL-1β) levels in cell culture supernatants were measured using ELISA.
- The impact of IL-1β on the NF-κB pathway in lung cancer cells was analyzed using proteome profiler arrays.
Main Results:
- Co-culturing lung cancer cells with macrophages led to significantly higher IL-1β expression compared to monocultures.
- IL-1β expression peaked at 24 hours and declined by the seventh day in co-cultures.
- IL-1β was found to activate the NF-κB pathway in H838 and H1975 lung cancer cells.
Conclusions:
- Lung cancer cell and macrophage interactions enhance IL-1β expression, suggesting a role in the tumor microenvironment.
- Dynamic IL-1β expression changes in vivo may influence lung cancer progression.
- Targeting IL-1β and its associated pathways presents a potential therapeutic strategy for lung cancer.
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