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]

IL32
Identifiers
AliasesIL32, IL-32alpha, IL-32beta, IL-32delta, IL-32gamma, NK4, TAIF, TAIFa, TAIFb, TAIFc, TAIFd, Interleukin 32, IL-32
External IDsOMIM: 606001 HomoloGene: 128400 GeneCards: IL32
Gene location (Human)
Chr.Chromosome 16 (human)[1]
Band16p13.3Start3,065,297 bp[1]
End3,082,192 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

9235

n/a

Ensembl

ENSG00000008517

n/a

UniProt

P24001

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 16: 3.07 – 3.08 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

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.

Function

This 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.[8]

IL-32 can also support osteoclast differentiation but not osteoclast activation by regulating the MAPK/ERK pathway and the actin cytoskeleton.[9]

Cancer

Cancer 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).[10]

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.[11][12]

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-kB (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.[11]

References
  1. GRCh38: Ensembl release 89: ENSG00000008517 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "Entrez Gene: Interleukin 32".
  4. Sloot YJ, Smit JW, Joosten LA, Netea-Maier RT (August 2018). "Insights into the role of IL-32 in cancer". Seminars in Immunology. 38: 24–32. doi:10.1016/j.smim.2018.03.004. PMID 29747940.
  5. Ribeiro-Dias F, Saar Gomes R, de Lima Silva LL, Dos Santos JC, Joosten LA (January 2017). "Interleukin 32: a novel player in the control of infectious diseases". Journal of Leukocyte Biology. 101 (1): 39–52. doi:10.1189/jlb.4RU0416-175RR. PMID 27793959.
  6. Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA (January 2005). "Interleukin-32: a cytokine and inducer of TNFalpha". Immunity. 22 (1): 131–42. doi:10.1016/j.immuni.2004.12.003. PMID 15664165.
  7. Dahl CA, Schall RP, He HL, Cairns JS (January 1992). "Identification of a novel gene expressed in activated natural killer cells and T cells". Journal of Immunology. 148 (2): 597–603. PMID 1729377.
  8. Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA (January 2005). "Interleukin-32: a cytokine and inducer of TNFalpha". Immunity. 22 (1): 131–42. doi:10.1016/j.immuni.2004.12.003. PMID 15664165.
  9. Mabilleau G, Sabokbar A (2009). "Interleukin-32 promotes osteoclast differentiation but not osteoclast activation". PLOS ONE. 4 (1): e4173. Bibcode:2009PLoSO...4.4173M. doi:10.1371/journal.pone.0004173. PMC 2613539. PMID 19137064.
  10. Hong JT, Son DJ, Lee CK, Yoon DY, Lee DH, Park MH (June 2017). "Interleukin 32, inflammation and cancer". Pharmacology & Therapeutics. 174: 127–137. doi:10.1016/j.pharmthera.2017.02.025. PMID 28223235. S2CID 26436008.
  11. Han S, Yang Y (March 2019). "Interleukin-32: Frenemy in cancer?". BMB Reports. 52 (3): 165–174. doi:10.5483/BMBRep.2019.52.3.019. PMC 6476484. PMID 30638183.
  12. Yan H, He D, Huang X, Zhang E, Chen Q, Xu R, et al. (July 2018). "Role of interleukin-32 in cancer biology". Oncology Letters. 16 (1): 41–47. doi:10.3892/ol.2018.8649. PMC 6006503. PMID 29930712.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.