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Interleukin 32
Interleukin 32 (IL32) is proinflammatory cytokine that in humans is encoded by the IL32 gene.[3] Interleukin 32 can be found in higher mammals but not in rodents. It is mainly expressed intracellularly and the protein has nine different isoforms, because the pre-mRNA can be alternatively spliced.[4][5] The most active and studied isoform is IL-32γ. It was first reported in 2005,[6] although the IL-32 gene was first described in 1992.[7] It does not belong to any cytokine family because there is almost no homology with other cytokines.[5] mRNA of IL-32 is mostly expressed in immune cells but also can be expressed in other tissues such as spleen, thymus, lung, small intestine, colon, prostate, heart, placenta, liver, muscle, kidney, pancreas and brain.[4][5] Interleukin 32 is connected with several diseases, including cancer. FunctionThis gene encodes a member of the cytokine family. The protein contains a tyrosine sulfation site, 3 potential N-myristoylation sites, multiple putative phosphorylation sites, and an RGD cell-attachment sequence. Expression of this protein is increased after the activation of T-cells by mitogens or the activation of NK cells by IL-2. This protein induces the production of TNF-alpha from macrophage cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[3] Interleukin 32 (IL-32) is a pro-inflammatory cytokine that can induce cells of the immune system (such as monocytes and macrophages) to secrete inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and IL-6. In addition, it can also induce the production of chemokines such as IL-8 and MIP-2 / CXCL2.[6] IL-32 can also support osteoclast differentiation but not osteoclast activation by regulating the MAPK/ERK pathway and the actin cytoskeleton.[8] CancerCancer is often connected with chronic infection and inflammation – they are cause of cancer in 25% of cases. IL-32 plays role in chronic inflammation process and in cancers connected with chronic inflammation (lung cancer, pancreatic cancer, cervical cancer and colon cancer).[9] IL-32 can be mainly found in cytoplasm of cancer cells. In various cancer tissues, IL32 is highly expressed and presently, the most common isoform of IL-32 found in cancer cells is IL-32β.[10][11] Function of IL-32 can be very different, depending on its isoform (different isoforms can interact with each other and influence their activities)[5] and type of cell, where it is expressed. IL-32 supports the tumor progression by cytokines expressed after activation of transcription factor NF-κB (nuclear factor-kB) and by metalloproteinase production. In addition, IL-32 stimulates differentiation into immunosuppressive cell types in some cancer types. These effects of IL-32 support tumor growth. On the other hand, in other cancer types it can also induce tumor cell apoptosis and enhance NK a cytotoxic T cell sensitivity which suppress tumor growth.[10] References
This article incorporates text from the United States National Library of Medicine, which is in the public domain. |
