Role of signal transduction pathways in IL-1β-induced apoptosis: Pathological and therapeutic aspects

Abstract

Background: Interleukin-1β (IL-1β) is a pro-inflammatory cytokine mainly produced by monocytes and macrophages with a wide range of biological effects. Evidence has shown that IL-1β plays a vital role in the process of apoptosis; however, the specific mechanisms, by which IL-1β induces apoptosis, vary due to different cellular and experimental conditions. Therefore, this present reviewstudy aimed to systematically review the association between the molecular mechanisms of IL-1β-induced apoptosis in pathological processes and the role of signaling pathways. This article also sought to briefly investigate the potential of signaling pathway-targeted therapy in the prevention and treatment of disease.

Methods: This is a literature review article. The present discourse aim is first to scrutinize and assess the available literature on IL-1β and apoptosis. The relevant studies using the keywords of "IL-1β-induced apoptosis" and "signaling pathways" were searched in the databases of PubMed, Scopus, Google Scholar, and Web of Science. Gathered relevant material, and extracted information was then assessed.

Results: IL-1β can induce apoptosis in various types of cells under different external stimuli via the mitochondrial pathway, death receptor pathway and endoplasmic reticulum pathway, and that the different pathways are often interconnected. The NF-kB signaling pathway, p38MAPK, and JNK signaling pathways mainly play a proapoptotic part, and the ERK1/2 pathway has a bidirectional role in regulating apoptosis, while activation of the PI3K-Akt signaling pathway can inhibit apoptosis.

Conclusion: This review indicates that IL-1β-induced apoptosis plays an important role in pathogenesis and development of pathology of many inflammatory diseases. Elucidating the role of the signaling pathways will aid the development of targeted therapeutic treatments.

Keywords: MAPKs signaling pathway; NF-κB signaling pathway; PI3K/Akt signaling pathway; apoptosis; interleukin-1β.

Figure 1

Role of signal transduction pathways in interleukin‐1β (IL‐1β)‐induced apoptosis. The nuclear factor‐κB (NF‐κB) signaling pathway, p38 mitogen‐activated protein kinase (p38MAPK), and c‐Jun N‐terminal kinase (JNK) signaling pathways mainly play a proapoptotic part, and the extracellular signal‐regulated protein kinase (ERK1/2) pathway has a bidirectional role in regulating apoptosis, while activation of the PI3K‐Akt signaling pathway can inhibit apoptosis.