Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2WYCW4)

DOT Name	Interleukin-26 (IL26)
Synonyms	IL-26; Protein AK155
Gene Name	IL26
Related Disease	Behcet disease ( ) Latent tuberculosis infection ( ) Rheumatoid arthritis ( ) Tuberculosis ( ) Type-1 diabetes ( ) Atopic dermatitis ( ) Chronic obstructive pulmonary disease ( ) Cowden disease ( ) Dermatitis ( ) Gastric disease ( ) Hepatocellular carcinoma ( ) Hidradenitis suppurativa ( ) Inflammatory bowel disease ( ) Leprosy ( ) Non-proliferative diabetic retinopathy ( ) Pleural tuberculosis ( ) Pneumonitis ( ) Proliferative diabetic retinopathy ( ) Psoriasis ( ) Skin disease ( ) Systemic sclerosis ( ) Ulcerative colitis ( ) Vasculitis ( ) Vitiligo ( ) X-linked reticulate pigmentary disorder ( ) Bronchiolitis obliterans syndrome ( ) Chronic graft versus host disease ( ) Allergic contact dermatitis ( ) Crohn disease ( ) Gastric cancer ( ) Granular corneal dystrophy type II ( ) Neoplasm ( ) Retinopathy ( ) Stomach cancer ( )
UniProt ID	IL26_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF00726
Sequence	MLVNFILRCGLLLVTLSLAIAKHKQSSFTKSCYPRGTLSQAVDALYIKAAWLKATIPEDR IKNIRLLKKKTKKQFMKNCQFQEQLLSFFMEDVFGQLQLQGCKKIRFVEDFHSLRQKLSH CISCASSAREMKSITRMKRIFYRIGNKGIYKAISELDILLSWIKKLLESSQ
Function	May play a role in local mechanisms of mucosal immunity and seems to have a pro-inflammatory function. May play a role in inflammatory bowel disease. Activates STAT1 and STAT3, MAPK1/3 (ERK1/2), JUN and AKT. Induces expression of SOCS3, TNF-alpha and IL-8, secretion of IL-8 and IL-10 and surface expression of ICAM1. Decreases proliferation of intestinal epithelial cells. Is inhibited by heparin.
Tissue Specificity	Expressed in HVS transformed T-cells but not other T-cell lines or primary stimulated T-cells. Expressed in colonic T-cells including Th17 inflammatory T-cells; the expression is significantly increased in serum of patients with Crohn's disease (at protein level).
KEGG Pathway	Cytokine-cytokine receptor interaction (hsa04060 ) JAK-STAT sig.ling pathway (hsa04630 )
Reactome Pathway	Interleukin-20 family signaling (R-HSA-8854691 )

Molecular Interaction Atlas (MIA) of This DOT

34 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Behcet disease	DISSYMBS	Definitive	Biomarker	[1]
Latent tuberculosis infection	DIS6R1EH	Definitive	Biomarker	[2]
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[3]
Tuberculosis	DIS2YIMD	Definitive	Biomarker	[2]
Type-1 diabetes	DIS7HLUB	Definitive	Genetic Variation	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[6]
Cowden disease	DISMYKCE	Strong	Biomarker	[7]
Dermatitis	DISY5SZC	Strong	Biomarker	[8]
Gastric disease	DISNZNTG	Strong	Altered Expression	[9]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[10]
Hidradenitis suppurativa	DIS3ZNAK	Strong	Biomarker	[11]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[3]
Leprosy	DISAA4UI	Strong	Biomarker	[12]
Non-proliferative diabetic retinopathy	DISPMG3Z	Strong	Altered Expression	[13]
Pleural tuberculosis	DISD09EG	Strong	Biomarker	[14]
Pneumonitis	DIS88E0K	Strong	Altered Expression	[15]
Proliferative diabetic retinopathy	DISQZ13G	Strong	Altered Expression	[13]
Psoriasis	DIS59VMN	Strong	Biomarker	[3]
Skin disease	DISDW8R6	Strong	Biomarker	[11]
Systemic sclerosis	DISF44L6	Strong	Altered Expression	[16]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[17]
Vasculitis	DISQRKDX	Strong	Altered Expression	[18]
Vitiligo	DISR05SL	Strong	Genetic Variation	[19]
X-linked reticulate pigmentary disorder	DIS0RB5A	Strong	Biomarker	[13]
Bronchiolitis obliterans syndrome	DISCK9IV	moderate	Biomarker	[20]
Chronic graft versus host disease	DIS1MM9J	moderate	Biomarker	[20]
Allergic contact dermatitis	DISFFVF9	Limited	Biomarker	[21]
Crohn disease	DIS2C5Q8	Limited	Biomarker	[7]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[9]
Granular corneal dystrophy type II	DISAEE20	Limited	Biomarker	[21]
Neoplasm	DISZKGEW	Limited	Altered Expression	[9]
Retinopathy	DISB4B0F	Limited	Biomarker	[22]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[9]
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⏷ Show the Full List of 34 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

3 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Interleukin-26 (IL26).	[23]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Interleukin-26 (IL26).	[24]
Dinoprostone	DMTYOPD	Approved	Dinoprostone decreases the expression of Interleukin-26 (IL26).	[25]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Interleukin-26 (IL26).	[26]
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References

1	Cytokine Signatures in Mucocutaneous and Ocular Behet's Disease.Front Immunol. 2017 Feb 27;8:200. doi: 10.3389/fimmu.2017.00200. eCollection 2017.
2	Microarray analysis of Mycobacterium tuberculosis-infected monocytes reveals IL26 as a new candidate gene for tuberculosis susceptibility.Immunology. 2015 Feb;144(2):291-301. doi: 10.1111/imm.12371.
3	Characterization of novel anti-IL-26 neutralizing monoclonal antibodies for the treatment of inflammatory diseases including psoriasis.MAbs. 2019 Nov-Dec;11(8):1428-1442. doi: 10.1080/19420862.2019.1654305. Epub 2019 Aug 18.
4	Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects.Hum Mol Genet. 2010 May 15;19(10):2059-67. doi: 10.1093/hmg/ddq078. Epub 2010 Feb 22.
5	Increased IL-26 Expression Promotes T Helper Type 17- and T Helper Type 2-Associated Cytokine Production by Keratinocytes in AtopicDermatitis.J Invest Dermatol. 2020 Mar;140(3):636-644.e2. doi: 10.1016/j.jid.2019.07.713. Epub 2019 Aug 26.
6	Pharmacological Modulation of Endotoxin-Induced Release of IL-26 in Human Primary Lung Fibroblasts.Front Pharmacol. 2019 Aug 30;10:956. doi: 10.3389/fphar.2019.00956. eCollection 2019.
7	IL26 modulates cytokine response and anti-TNF consumption in Crohn's disease patients with bacterial DNA.J Mol Med (Berl). 2017 Nov;95(11):1227-1236. doi: 10.1007/s00109-017-1585-6. Epub 2017 Sep 6.
8	Biological Effects of IL-26 on T Cell-Mediated Skin Inflammation, Including Psoriasis.J Invest Dermatol. 2019 Apr;139(4):878-889. doi: 10.1016/j.jid.2018.09.037. Epub 2018 Nov 10.
9	Investigation on correlations of serum IL-26 with diagnosis and staging of gastric cancer.J BUON. 2019 Jan-Feb;24(1):215-220.
10	Expression of IL-26 predicts prognosis of patients with hepatocellular carcinoma after surgical resection.Hepatobiliary Pancreat Dis Int. 2019 Jun;18(3):242-248. doi: 10.1016/j.hbpd.2019.03.006. Epub 2019 Mar 27.
11	A new T helper 17 cytokine in hidradenitis suppurativa: antimicrobial and proinflammatory role of interleukin-26.Br J Dermatol. 2019 Nov;181(5):1038-1045. doi: 10.1111/bjd.17854. Epub 2019 Jun 23.
12	IL-26 contributes to host defense against intracellular bacteria.J Clin Invest. 2019 Apr 2;129(5):1926-1939. doi: 10.1172/JCI99550. eCollection 2019 Apr 2.
13	Increased interleukin-26 expression in proliferative diabetic retinopathy.Int J Ophthalmol. 2019 Nov 18;12(11):1688-1692. doi: 10.18240/ijo.2019.11.04. eCollection 2019.
14	Interleukin-26 upregulates interleukin-22 production by human CD4(+) T cells in tuberculous pleurisy.J Mol Med (Berl). 2019 May;97(5):619-631. doi: 10.1007/s00109-018-01741-1. Epub 2019 Mar 5.
15	IL-26 in the induced sputum is associated with the level of systemic inflammation, lung functions and body weight in COPD patients.Int J Chron Obstruct Pulmon Dis. 2018 Aug 24;13:2569-2575. doi: 10.2147/COPD.S164833. eCollection 2018.
16	The elevated expression of Th17-related cytokines and receptors is associated with skin lesion severity in early systemic sclerosis.Hum Immunol. 2015 Jan;76(1):22-9. doi: 10.1016/j.humimm.2014.12.008. Epub 2014 Dec 11.
17	Interleukin (IL)-22 from IL-20 Subfamily of Cytokines Induces Colonic Epithelial Cell Proliferation Predominantly through ERK1/2 Pathway.Int J Mol Sci. 2019 Jul 15;20(14):3468. doi: 10.3390/ijms20143468.
18	IL-26 Confers Proinflammatory Properties to Extracellular DNA.J Immunol. 2017 May 1;198(9):3650-3661. doi: 10.4049/jimmunol.1600594. Epub 2017 Mar 29.
19	Association analysis of class II cytokine and receptor genes in vitiligo patients.Hum Immunol. 2016 May;77(5):375-81. doi: 10.1016/j.humimm.2015.09.050. Epub 2015 Sep 30.
20	Regulation of pulmonary graft-versus-host disease by IL-26+CD26+CD4 T lymphocytes.J Immunol. 2015 Apr 15;194(8):3697-712. doi: 10.4049/jimmunol.1402785. Epub 2015 Mar 18.
21	IL-26 in allergic contact dermatitis: Resource in a state of readiness.Exp Dermatol. 2018 Jun;27(6):681-684. doi: 10.1111/exd.13521. Epub 2018 Apr 10.
22	RETRACTED: Anti-angiogenic effect of Interleukin-26 in oxygen-induced retinopathy mice via inhibiting NFATc1-VEGF pathway.Biochem Biophys Res Commun. 2018 May 23;499(4):849-855. doi: 10.1016/j.bbrc.2018.04.004. Epub 2018 Apr 4.
23	Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
24	Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
25	Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med. 2009 Mar 16;206(3):535-48. doi: 10.1084/jem.20082293. Epub 2009 Mar 9.
26	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.