IL-33 synergistically promotes the proliferation of lung cancer cells in vitro by inducing antibacterial peptide LL-37 and proinflammatory cytokines in macrophages.
Jiang. Yinting Y; Liao. Hongyi H; Zhang. Xuemei X; Cao. Sijia S; Hu. Xuexue X; Yang. Zihan Z; Fang. Yuting Y; Wang. Hong H
Key Findings
- IL‑33 stimulates macrophages to produce more LL‑37.
- LL‑37 together with IL‑33 boosts inflammatory cytokines IL‑6 and IL‑1β.
- The combined effect of IL‑33 and LL‑37 increases lung cancer cell proliferation in vitro.
Practical Outcomes
- For biohackers, the research suggests that raising LL‑37 (or IL‑33) is not beneficial and could potentially worsen lung cancer risk. There are no direct dosing or supplementation recommendations, but it cautions against interventions that might unintentionally boost these inflammatory pathways, especially for people with a predisposition to lung cancer.
Summary
The study found that a protein called IL‑33 makes immune cells release more of the antimicrobial peptide LL‑37, which then ramps up inflammation (IL‑6 and IL‑1β) and makes lung cancer cells grow faster in a dish. In short, higher LL‑37 levels, driven by IL‑33, appear to help lung cancer cells multiply.
Abstract
Lung cancer is the primary cause of cancer-related deaths, and the persistent inflammation is inextricably linked with the lung cancer tumorigenesis. Pro-inflammatory cytokine interleukin-33 (IL-33) is able to serve as a potent modulator of cancer. Mounting evidence indicates IL-33 has significant effect on lung cancer progression by regulating host immune response, but the current opinions about the function and mechanism of IL-33 in lung cancer are still controversial. Meanwhile, antibacterial peptide LL-37 also exerts a momentous effect on immune responses to lung cancer. LL-37 is regarded as versatile, including antimicrobial activities, chemotaxis and immunoregulation. However, the immunomodulatory mechanism of IL-33 and LL-37 in lung cancer remains thoroughly not defined. Here, we determined the secretion of LL-37 was up-regulated in lung cancer serum samples. Similarly, the expression of CRAMP was enhancive in macrophages after co-cultured with lung cancer cells. Moreover, we expounded that IL-33 could up-regulate LL-37 secretion in macrophages, resulting in the massive releases of IL-6 and IL-1β. Additionally, LL-37 cooperated with IL-33 to increase the phosphorylation of p38 MAPK and NF-κB p65 pathways, and augmented IL-6 and IL-1β secretion, which resulting in the proliferation of lung cancer cells in vitro. In conclusion, our study identified that IL-33 aggravated the inflammation of lung cancer by increasing LL-37 expression in macrophages, thereby promoting lung cancer cell proliferation in vitro. It is contributed to our present understanding of the immunomodulatory relationship between pro-inflammatory cytokines and antibacterial peptides in the tumor immune response, and offer a novel perspective for controlling the progress of lung cancer.
Study Information
pubmed
2020
2020-11-03T00:00:00.000Z
10.1016/j.imbio.2020.152025
11
51