Interleukin 32, inflammation and cancer

Abstract

Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues. The IL-32 transcript is expressed in various human tissues and organs such as the spleen, thymus, leukocyte, lung, small intestine, colon, prostate, heart, placenta, liver, muscle, kidney, pancreas, and brain. Cytokines are critical components of cell signaling pathways that are involved in the regulation of cell growth, metabolism, hormone signaling, immune regulation and a variety of other physiological functions. Earlier studies have demonstrated that IL-32 regulates cell growth, metabolism and immune regulation and is therefore involved in the pathologic regulator or protectant of inflammatory diseases. Previous studies defined that IL-32 is upregulated in the patients with several inflammatory diseases, and is induced by inflammatory responses. However, several reports suggested that IL-32 is downregulated in several inflammatory diseases including asthma, HIV infection disease, neuronal diseases, metabolic disorders, experimental colitis and metabolic disorders. IL-32 is also involved in various cancer malignancies including renal cancer, esophageal cancer and hepatocellular carcinoma, lung cancer, gastric cancer, breast cancer, pancreatic cancer, lymphoma, osteosarcoma, breast cancer, colon cancer and thyroid carcinoma. Other studies suggested that IL-32 decreases tumor development including cervical cancer, colon cancer and prostate cancer, melanoma, pancreatic cancer, liver cancer and chronic myeloid leukemia. Nevertheless, review articles that discuss the roles and its mechanism of IL-32 isoforms focusing on the therapeutic approaches have not yet been reported. In this review article, we will discuss recent findings regarding IL-32 in the development of diseases and further discuss therapeutic approaches targeting IL-32. Moreover, we will suggest that IL-32 could be the target of several diseases and the therapeutic agents for targeting IL-32 may have potential beneficial effects for the treatment of inflammatory diseases and cancers. Future research should open new avenues for the design of novel therapeutic approaches targeting IL-32.

Keywords: Cancer; Cytokine; Inflammatory disease; Interleukin-32 (IL-32); Spliced isoforms; Therapeutic approaches.