IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis

Abstract

A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32β, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1β as well as macrophage inflammatory protein-2 (MIP-2) and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD), gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems.

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

“…IL-32 gene was found to be located on human chromosome 16p13.3 and was reported to exist in nine different isoforms by mRNA alternative splicing including IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , IL-32 , and IL-32 s (small), with specific activities and properties. Moreover, these isoforms can interact with each other intracellularly to control their respective activities and IL-32 is the most active isoform [105][106][107]. IL-32 is not assigned to any of the cytokine families, due to the lack of homology with other well-known cytokines.…”

MHC class II associated stomach cancer mutations correlate with lack of subsequent tumor development

“…The issue of the variable impacts of immune function spans the consideration of the role of the immune system in tumor development. Immune checkpoint inhibitors have had great positive benefits for at least a subset of patients (18), yet in other settings, evidence indicates that inflammation, particularly chronic inflammation, is associated with tumor development (19,20).…”

Interleukin-32 Gamma as a New Face in Inflammatory Bone Diseases

“…There are 9 different splice variants in humans: IL-32α, IL-32β, [34][35][36][37][38] Chronic inflammation and autoimmune disease Elevated IL-32 level in chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis (CRS), inflammatory bowel disease [9,13,39,40] Inflammatory bone disease Rheumatoid arthritis (RA), ankylosing spondylitis (AS), osteoporosis [3][4][5] IL-32γ, IL-32δ, IL-32ε, IL-32ξ, IL-32η, IL-32θ, and IL-32ζ [6], and different isoforms of IL-32 have diverse biological functions. IL-32 is now recognized as a proinflammatory cytokine produced in epithelial cells, NK cells, CD4 + T cells, and synovial fibroblasts in response to various cytokines such as IL-1β, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-6, IL-8, IL-12, and IL-18 [12][13][14].…”

“…It has been studied in various clinical fields ranging from infectious diseases, chronic inflammation, autoimmune diseases, and cancers [7][8][9][10][11] (Table 1).…”

“…IL-32 is now defined as a multi-faceted cytokine involved in infections, cancer, chronic inflammation, and autoimmune disease [7][8][9][10][11]. Recent evidences have begun to shed light on the physiological role of IL-32γ in pathogenic changes of bone, thereby providing a means to grasp the underlying pathogenesis of human inflammatory bone diseases.…”