A panoramic spectrum of complex interplay between the immune system and IL-32 during pathogenesis of various systemic infections and inflammation (original) (raw)
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Interleukin-32 in Inflammatory Autoimmune Diseases
Immune Network, 2014
Interleukin-32 (IL-32) is a cytokine inducing crucial inflammatory cytokines such as tumor necrosis factor-α (TNFα) and IL-6 and its expression is elevated in various inflammatory autoimmune diseases, certain cancers, as well as viral infections. IL-32 gene was first cloned from activated T cells, however IL-32 expression was also found in other immune cells and non-immune cells. IL-32 gene was identified in most mammals except rodents. It is transcribed as multiple-spliced variants in the absence of a specific activity of each isoform. IL-32 has been studied mostly in clinical fields such as infection, autoimmune, cancer, vascular disease, and pulmonary diseases. It is difficult to investigate the precise role of IL-32 in vivo due to the absence of IL-32 gene in mouse. The lack of mouse IL-32 gene restricts in vivo studies and restrains further development of IL-32 research in clinical applications although IL-32 new cytokine getting a spotlight as an immune regulatory molecule processing important roles in autoimmune, infection, and cancer. In this review, we discuss the regulation and function of IL-32 in inflammatory bowel diseases and rheumatoid arthritis.
Immunology, 2009
A proinflammatory cytokine interleukin-32b promotes the production of an anti-inflammatory cytokine interleukin-10 Introduction Interleukin-32 (IL-32), originally reported as natural killer (NK) transcript 4, which was the IL-32c isoform, is produced by activated T cells and NK cells and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. 1 However, the function of IL-32 has been unclear. Recently, IL-32 was defined as a proinflammatory cytokine that is induced in epithelial cells and monocytes by interferon-c (IFN-c) stimulation in a time-dependent manner. 2-4 Moreover, proteinase 3 has been identified as an IL-32a binding protein that produces the active form of IL-32a. Cleavage of IL-32a by proteinase 3 induces macrophage inflammatory protein-2 in mouse Raw264.7 cells and IL-8 in human peripheral blood mononuclear cells (PBMC). 5 These observations suggest that IL-32 belongs to a proinflammatory cytokine group. Six alternatively spliced isoforms of IL-32 have been reported, 3,6,7 but the functional differences among the isoforms have not been elucidated.
Mediators of Inflammation, 2016
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-1βas 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...
American journal of translational research, 2017
Interleukin-32 theta (IL-32θ) is newly identified isoform of IL-32 which plays a vital role in inflammatory responses. Like IL-32α and IL-32β, IL-32θ isoform acts as an intracellular inflammatory modulator. It results in reduction of IL-1β production by attenuating the expression of PU.1 and inhibition of monocytes differentiation into macrophages. IL-32θ hinders TNF-α expression by inhibiting p38 MAPK and inhibitor of κB (IκB) as well. It also reserved STAT3-ZEB1 pathway leading to the inhibition of epithelial-mesenchymal transition (EMT) and stemness. Hence, it can be concluded that IL-32θ is an anti-inflammatory cytokine that can act as a tumor suppressor and can play vital role in colon cancer therapies. IL-32θ also plays a crucial role in immune system responses and cellular differentiation during disease pathogenesis. To our best knowledge this is the first ever review to condense the importance, precise mode of action in disease progression and latent remedial implications of...
Identification of the most active interleukin-32 isoform
Immunology, 2009
Cytokines are crucial in host defence against pathogens such as bacteria, viruses, fungi and parasites. A newly described cytokine, interleukin-32 (IL-32), induces various proinflammatory cytokines (tumour necrosis factor-a, IL-1b, IL-6) and chemokines in both human and mouse cells through the nuclear factor-jB and p38 mitogen-activated protein kinase inflammatory signal pathway. The IL-32 primarily acts on monocytic cells rather than T cells. In an attempt to isolate the IL-32 soluble receptor, we used an IL-32 ligand-affinity column to purify neutrophil proteinase 3, which is a serine proteinase involved in many inflammatory diseases. IL-32 has biological activity associated with Mycobacterium tuberculosis and chronic proinflammatory diseases such as rheumatoid arthritis. IL-32 is transcribed as six alternative splice variants and the biological activity of each individual isoform remains unknown. Here, we cloned the complementary DNA of the four IL-32 isoforms (a, b, c and d) that are the most representative IL-32 transcripts. To produce recombinant protein with a high yield, the amino acids of two cysteine residues were mutated to serine residues, because serine residues are not conserved among different species. The multi-step purified recombinant IL-32 isoform proteins were assessed for their biological activities with different cytokine assays. The c isoform of IL-32 was the most active, although all isoforms were biologically active. The present study will provide a specific target to neutralize endogenous IL-32, which may contribute to basic and clinical immunology.
IL-32, a Novel Proinflammatory Cytokine in Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, 2008
Scientific knowledge on the subject COPD is characterised by an exaggerated immune response, but the mechanisms of this response are yet unknown. IL-32 has recently been proposed as a possible regulator of innate and adaptive responses, particularly in inflammatory diseases.
Interleukin-32δ interacts with IL-32β and inhibits IL-32β-mediated IL-10 production
FEBS Letters, 2013
Structured summary of protein interactions: PKC delta physically interacts with IL-32 beta by anti bait coimmunoprecipitation (View interaction) IL-32 beta physically interacts with PKC delta by anti tag coimmunoprecipitation (View interaction) IL-32 beta physically interacts with IL-32 delta by anti tag coimmunoprecipitation (1, 2) PKC delta and IL-32 beta colocalize by fluorescence microscopy (view interaction)
IL-31 a TH2 Cytokine Involved in Immunity and Inflammation
International Journal of Immunopathology and Pharmacology, 2010
Cytokines are immunal regulatory proteins, however they also play a relevant role in inflammatory diseases. IL-31 is a newly discovered cytokine expressed primarily in TH2 cells, introduced by activated CD4+ T cells. IL-31 is capable of inducing chemokines and other cytokines in several inflammatory diseases via its surface receptor. This cytokine is also produced by mast cells and mast cell line, suggesting a role in allergic diseases. In this editorial we revisit the biological role of IL-31 in immunity and inflammation.