Interleukin-32

Interleukins (from Latin/Greek inter = between; leukos = white; kinein = to move) are a group of endogenous, short-chain regulatory proteins (cytokines) of the immune system (IL1-IL38). Interleukins are mediators for induction, course and control of T-cell-mediated cytotoxic immune reactions as well as B-cell activation (antibody production). They are mainly formed and secreted by stimulated leukocytes, monocytes and macrophages. So far, about 38 different interleukins have been clearly identified. Each cytokine of the interleukin group is nomenclatically assigned a number for its classification (IL-1 to IL-38 - status 2017).

Some structurally related substances have been grouped into families. Their members often have a similar function or participate in the fine regulation of immune reactions, for example by regulating the synthesis of related interleukins.

Interleukin-32 (IL-32) is a new proinflammatory cytokine that has only been known since 2005 and was originally described as a transcript (NK4) that was selectively expressed by activated NK cells or T cells. Interleukin-32 is encoded by the IL32 gene. Known are 4 (6) isoforms of interleukin-32; others are expected to be

Due to its exceptional protein folding structure, the IL-32 molecule does not show homologies with the known inflammatory cytokine families. It can therefore be classified as a new type of inflammatory cytokine, which is known to activate the signalling pathways of the nuclear factor-kappaB NF-κBm and the p38 mitogen-activate protein kinase MAPK.

The cytokine is produced and secreted in T cells, NK cells, monocytes, macrophages and fibroblasts (lung fibroblasts). Interleukin-32 activates monocytes, macrophages, epithelia and fibroblasts, which on the basis of this stimulus form inflammatory cytokines such as the "tumor necrosis factor-alpha" TNF-alpha, the interleukins -6 and -8 as well as the chemokines MIP-2/CXCL2.

Interleukin-32 is expressed in various diseases such as chronic inflammatory diseases like COPD and bronchial asthma (Li et al. 2015), autoimmune diseases, various tumor types, viral and bacterial infections (Kim 2014).

IL-32 and IL-32 mRNA are overexpressed in Helicobacter pylori-infected epithelial cell lines of gastric gastric mucosa and are thus likely to play a pathogenetic role via consecutive cytokine production.

IL-32 may further contribute to the differentiation of osteoclasts.

Interleukin-32 is expressed in rheumatoid arthritis in synovial tissue. After injection of IL-32 into the knee joint of mice, inflammatory arthritis develops.

IL-32 is further induced by Mycobacterium tuberculosis and Mycobacterium bovis as well as by the cytomegalovirus, whereby the production induced by M. tuberculosis is dependent on endogenous interferon-gamma (IFN-γ).

Interleukin 32 is used in various diseases. Malignomas, interleukin 32 is overexpressed in gastric cancer. In the tumor epithelia the cytokine VEGF, the matrix metalloproteinases 2 and 9 (MMP2, MMP9) as well as the hypoxia-iducible-factor 1 alpha" HIF-1alpha are induced (Tsai et al. 2014).

Bai X et al.(2015) The role of interleukin-32 against tuberculosis. Cytokines 76:585-587.

Huang Y et al (201) The expression of interleukin-32 is activated by human cytomegalovirus infection and down regulated by hcmv-miR-UL112-1. virol J 10:51.

Joosten LA et al (2013) Novel insights into the biology of interleukin-32 Cell Mol Life Sci 70:3883-3892.

Li D et al (2015) c-Jun N-terminal kinase and Akt signalling pathways regulating tumour necrosis factor-α-induced interleukin-32 expression in human lung fibroblasts: implications in airway inflammation. Immunology 144:282-290.

Kim S (2014) Interleukin-32 in inflammatory autoimmune diseases. Immune Netw 14:123-127.

Peng LS et al (2014) Elevated interleukin-32 expression is associated with Helicobacter pylori-related gastritis. PLoS One 9:e88270.

Tsai CY et al (2014) Interleukin-32 increases human gastric cancer cell invasion associated with tumor progression and metastasis. Clin Cancer Res 20:2276-2288.