Interleukin 32 (IL32) is proinflammatorycytokine that in humans is encoded by theIL32gene.[3] Interleukin 32 can be found in highermammals but not inrodents. It is mainly expressed intracellularly and theprotein has nine differentisoforms, because thepre-mRNA can bealternatively spliced.[4][5] The most active and studied isoform is IL-32γ. It was first reported in 2005,[6] although theIL-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 inimmune 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, includingcancer.
This gene encodes a member of thecytokine family. The protein contains a tyrosine sulfation site, 3 potentialN-myristoylation sites, multiple putativephosphorylation sites, and anRGD cell-attachment sequence. Expression of this protein is increased after the activation ofT-cells bymitogens or the activation ofNK cells byIL-2. This protein induces the production ofTNF-alpha frommacrophage cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[3]
Interleukin 32 (IL-32) is a pro-inflammatorycytokine that can induce cells of theimmune system (such asmonocytes andmacrophages) to secrete inflammatory cytokines, such astumor necrosis factor-alpha (TNF-α) and IL-6. In addition, it can also induce the production ofchemokines such asIL-8 and MIP-2 /CXCL2.[6]
IL-32 can also supportosteoclast differentiation but not osteoclast activation by regulating theMAPK/ERK pathway and the actin cytoskeleton.[8]
Cancer is often connected with chronicinfection andinflammation – 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 andcolon cancer).[9]
IL-32 can be mainly found incytoplasm 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 bycytokines expressed after activation of transcription factorNF-κB (nuclear factor-kB) and bymetalloproteinase 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 cellapoptosis and enhanceNK acytotoxic T cell sensitivity which suppress tumor growth.[10]
This article incorporates text from theUnited States National Library of Medicine, which is in thepublic domain.