Interleukin 32

Last updated
IL32
Identifiers
Aliases IL32 , IL-32alpha, IL-32beta, IL-32delta, IL-32gamma, NK4, TAIF, TAIFa, TAIFb, TAIFc, TAIFd, Interleukin 32, IL-32
External IDs OMIM: 606001 HomoloGene: 128400 GeneCards: IL32
Orthologs
SpeciesHumanMouse
Entrez

9235

n/a

Ensembl

ENSG00000008517

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UniProt

P24001

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RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

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

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.

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. [6]

IL-32 can also support osteoclast differentiation but not osteoclast activation by regulating the MAPK/ERK pathway and the actin cytoskeleton. [8]

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). [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]

Related Research Articles

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Interleukin 12</span> Interleukin

Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.

<span class="mw-page-title-main">Interleukin 4</span> Mammalian protein found in Mus musculus

The interleukin 4 is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13.

<span class="mw-page-title-main">RANKL</span> Mammalian protein found in Homo sapiens

Receptor activator of nuclear factor kappa-Β ligand (RANKL), also known as tumor necrosis factor ligand superfamily member 11 (TNFSF11), TNF-related activation-induced cytokine (TRANCE), osteoprotegerin ligand (OPGL), and osteoclast differentiation factor (ODF), is a protein that in humans is encoded by the TNFSF11 gene.

<span class="mw-page-title-main">Interleukin 15</span> Cytokine with structural similarity to Interleukin-2

Interleukin-15 (IL-15) is a protein that in humans is encoded by the IL15 gene. IL-15 is an inflammatory cytokine with structural similarity to Interleukin-2 (IL-2). Like IL-2, IL-15 binds to and signals through a complex composed of IL-2/IL-15 receptor beta chain (CD122) and the common gamma chain. IL-15 is secreted by mononuclear phagocytes following infection by virus(es). This cytokine induces the proliferation of natural killer cells, i.e. cells of the innate immune system whose principal role is to kill virally infected cells.

Interleukin 27 (IL-27) is a member of the IL-12 cytokine family. It is a heterodimeric cytokine that is encoded by two distinct genes, Epstein-Barr virus-induced gene 3 (EBI3) and IL-27p28. IL-27 is expressed by antigen presenting cells and interacts with a specific cell-surface receptor complex known as IL-27 receptor (IL-27R). This receptor consists of two proteins, IL-27Rɑ and gp130. IL-27 induces differentiation of the diverse populations of T cells in the immune system and also upregulates IL-10.

<span class="mw-page-title-main">Interleukin 24</span> Protein-coding gene in the species Homo sapiens

Interleukin 24 (IL-24) is a protein in the interleukin family, a type of cytokine signaling molecule in the immune system. In humans, this protein is encoded by the IL24 gene.

<span class="mw-page-title-main">Interleukin 20</span> Protein-coding gene in the species Homo sapiens

Interleukin 20 (IL20) is a protein that is in humans encoded by the IL20 gene which is located in close proximity to the IL-10 gene on the 1q32 chromosome. IL-20 is a part of an IL-20 subfamily which is a part of a larger IL-10 family.

<span class="mw-page-title-main">Interleukin 17</span> Group of proteins

Interleukin 17 family is a family of pro-inflammatory cystine knot cytokines. They are produced by a group of T helper cell known as T helper 17 cell in response to their stimulation with IL-23. Originally, Th17 was identified in 1993 by Rouvier et al. who isolated IL17A transcript from a rodent T-cell hybridoma. The protein encoded by IL17A is a founding member of IL-17 family. IL17A protein exhibits a high homology with a viral IL-17-like protein encoded in the genome of T-lymphotropic rhadinovirus Herpesvirus saimiri. In rodents, IL-17A is often referred to as CTLA8.

<span class="mw-page-title-main">Interleukin 19</span> Protein-coding gene in the species Homo sapiens

Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.

Understanding of the antitumor immunity role of CD4+ T cells has grown substantially since the late 1990s. CD4+ T cells (mature T-helper cells) play an important role in modulating immune responses to pathogens and tumor cells, and are important in orchestrating overall immune responses.

<span class="mw-page-title-main">Toll-like receptor 4</span> Protein-coding gene in the species Homo sapiens

Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an intracellular signaling pathway NF-κB and inflammatory cytokine production which is responsible for activating the innate immune system.

<span class="mw-page-title-main">CEBPB</span> Protein-coding gene in the species Homo sapiens

CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.

<span class="mw-page-title-main">Interleukin-4 receptor</span> Protein-coding gene in the species Homo sapiens

The interleukin 4 receptor is a type I cytokine receptor. It is a heterodimer, that is, composed of two subunits. IL4R is the human gene coding for IL-4Rα, the subunit which combines with either common gamma chain or with IL-13Rα1.

<span class="mw-page-title-main">Colony stimulating factor 1 receptor</span> Protein found in humans

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.

<span class="mw-page-title-main">PRDM1</span> Protein-coding gene in the species Homo sapiens

PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene PRDM1 located on chromosome 6q21. BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and plays a critical role in the development of plasma B cells, T cells, dendritic cells (DCs), macrophages, and osteoclasts. Pattern Recognition Receptors (PRRs) can activate BLIMP-1, both as a direct target and through downstream activation. BLIMP-1 is a transcription factor that triggers expression of many downstream signaling cascades. As a fine-tuned and contextual rheostat of the immune system, BLIMP-1 up- or down-regulates immune responses depending on the precise scenarios. BLIMP-1 is highly expressed in exhausted T-cells – clones of dysfunctional T-cells with diminished functions due to chronic immune response against cancer, viral infections, or organ transplant.

<span class="mw-page-title-main">CD200</span> Protein-coding gene in the species Homo sapiens

OX-2 membrane glycoprotein, also named CD200 is a human protein encoded by the CD200 gene. CD200 gene is in human located on chromosome 3 in proximity to genes encoding other B7 proteins CD80/CD86. In mice CD200 gene is on chromosome 16.

An inflammatory cytokine or proinflammatory cytokine is a type of signaling molecule that is secreted from immune cells like helper T cells (Th) and macrophages, and certain other cell types that promote inflammation. They include interleukin-1 (IL-1), IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF-α), interferon gamma (IFNγ), and granulocyte-macrophage colony stimulating factor (GM-CSF) and play an important role in mediating the innate immune response. Inflammatory cytokines are predominantly produced by and involved in the upregulation of inflammatory reactions.

<span class="mw-page-title-main">Interleukin-1 family</span> Group of cytokines playing a key role in the regulation of immune and inflammatory responses

The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.

<span class="mw-page-title-main">Interleukin 17F</span>

Interleukin 17F (IL-17F) is signaling protein that is in human is encoded by the IL17F gene and is considered a pro-inflammatory cytokine. This protein belongs to the interleukin 17 family and is mainly produced by the T helper 17 cells after their stimulation with interleukin 23. However, IL-17F can be also produced by a wide range of cell types, including innate immune cells and epithelial cells.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000008517 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 1 2 "Entrez Gene: Interleukin 32".
  4. 1 2 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. S2CID   13666063.
  5. 1 2 3 4 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. 1 2 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. doi:10.4049/jimmunol.148.2.597. PMID   1729377.
  8. ↑ 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.
  9. ↑ 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.
  10. 1 2 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.
  11. ↑ 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.

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