Interleukin 24

Source: Wikipedia, the free encyclopedia.
IL24
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_001185156
NM_001185157
NM_001185158
NM_006850
NM_181339

NM_053095

RefSeq (protein)

NP_001172085
NP_001172086
NP_001172087
NP_006841

NP_444325

Location (UCSC)Chr 1: 206.9 – 206.9 MbChr 1: 130.81 – 130.82 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

IL-24 is a

T helper 2 (Th2) cells[5] and acts on skin, lung, and reproductive tissues. IL-24 performs important roles in wound healing, arthritis, psoriasis and cancer.[6][7][8] Several studies have shown that cell death occurs in cancer cells/cell lines following exposure to IL-24.[9][10] The gene for IL-24 is located on chromosome 1 in humans.[11]

Structure

The structure of IL-24 has been found through crystallization by fusing a flexible linker with a ligand to its two receptors, IL-22R1 and IL-20R2. The structure revealed that there is a lack of disulfides, which is present in most cytokines, and is likely the reason why IL-24 is unstable compared to other interleukins.[12]

IL-24 is a secreted protein that is highly conserved throughout evolution with

splice variants of IL-24 lacking one or more exons.[13] The signal peptide in IL-24 is two times the length as in other related human cytokines (51 amino acids), and the predicted molecular mass of IL-24 monomer is 18.3 kDa.[14]

Function

IL-24 functions as a

or spondyloarthropathy.

IL-24's Role in the Jak/STAT Pathway

IL-24 carries its functions through two types of membrane receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2) with simultaneous activation of the JAK/signal transducer and activator of transcription (STAT) pathway within their cytoplasmic domains.[16] IL-24 is a type of cytokine that interacts frequently with class 2 cytokine receptors. IL-24 can form IL-20R1/IL-20R2 and IL-22R1/IL-20R2 which are shared with the other IL-20SFCs and IL-22. IL-20SFC is an IL-20 subfamily of cytokines which includes IL-19, IL-20, and IL-24. They all signal through the common chain that is IL-20R2. Through these two types of membrane receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2), simultaneous activation of the JAK/signal transducer and activator of transcription (STAT) pathway within their cytoplasmic domains.[16]

Although it belongs to the same group of cytokines as IL-10, it has different effect on the immune system. IL-10 is a suppressive cytokine that suppresses inflammation while also maintaining immunomodulatory functions. Beside the normal physiological roles, IL-24 inhibits tumor growth, invasion, metastasis and angiogenesis.[17]

Production of IL-24 by Different Cells

IL-24 can be produced by

myeloid cells (in response to microbial products through TLRs), lymphoid cells, and epithelial cells in response to cytokine stimulation. IL-24 can also dampen the first rounds of CD8 cell expansion to prevent uncontrolled T cell responses. After the combination of anti-IgM and CD40-L stimulation, B lymphocytes can also induce IL-24 expression. In response to immune cells, non-lymphoid cells such as melanocytes can also produce IL-24.[18]

Cancer

IL-24 is an immunomodulatory cytokine which can also display broad cancer-specific suppressor effects. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, sensitization to chemotherapy, and induction of cancer-specific apoptosis. Given its ubiquitous apoptotic effect on malignant cells, lack of an effect on normal cells, and absence of significant side effects, IL-24 is an important candidate for cancer therapy.[19]

IL-24 is able to induce apoptosis via both intracellular and extracellular signaling mechanisms. Secreted IL-24 protein induces a robust expression of endogenous IL-24 and subsequent induction of tumor-specific killing through an ER stress-mediated pathway as well as by ROS production. The ER stress is the initial pathway in IL-24-induced apoptosis.[19]

An important question, which remained unresolved, is why IL-24 has the abilities to selectively induce apoptosis in a large spectrum of human cancer-derived cell lines without harming normal cells. One possible reason for this differential killing effect involves inherent biochemical differences between normal and cancer cells (ER stress, ROS production and ceramide), another possibility is that IL-24 is able to target a molecule that only triggers apoptosis in cancer cells. The third option for this differential killing effect is that both of the above hypotheses are correct.[19]

IL-24 is able to induce toxic autophagy in cancer cells in vitro and animal models in vivo. Past independent studies have also proven that the cytokine can play a role in inflammation for inflammatory bowel disease, psoriasis, cardiovascular disease, rheumatoid arthritis, tuberculosis, and viral infection.[20]

Secondary cytokines that evoke antitumor immune responses are stimulated by IL-24. These secondary cytokines include

Src, a proto-oncogene, within tumor cells and inhibiting epithelial cell differentiation.[22] IL-24 also induces apoptosis By inducing more stress on the endoplasmic reticulum.[23]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162892 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026420 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. S2CID 1329942
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  8. PMID 26968800.{{cite journal}}: CS1 maint: DOI inactive as of February 2024 (link
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  11. ^ IL24 GeneCard
  12. PMID 30111632
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    PMID 27271601. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License
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External links