Details of Drug Off-Target (DOT)

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

• DOT Name: Interleukin-1 family member 10 (IL1F10)
• Synonyms: IL-1F10; Family of interleukin 1-theta; FIL1 theta; Interleukin-1 HY2; IL-1HY2; Interleukin-1 theta; IL-1 theta; Interleukin-38; IL-38
• Gene Name: IL1F10
• Related Disease:
  Arthritis
  Advanced cancer
  Allergic asthma
  Ankylosing spondylitis
  Arteriosclerosis
  Asthma
  Atherosclerosis
  Autoimmune disease
  Colitis
  Corneal neovascularization
  Crohn disease
  Dermatitis
  Hidradenitis suppurativa
  Hyperlipidemia
  Lung adenocarcinoma
  Lung cancer
  Myocardial infarction
  Non-small-cell lung cancer
  Obesity
  Psoriasis
  Psoriatic arthritis
  Pustular psoriasis
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Systemic sclerosis
  Colorectal carcinoma
  Retinopathy
  Acute myelogenous leukaemia
  Glaucoma/ocular hypertension
  Inflammatory bowel disease
  Neoplasm
• UniProt ID: IL1FA_HUMAN
• PDB ID: 5BOW
• Pfam ID: PF00340
• Sequence:
  MCSLPMARYYIIKYADQKALYTRDGQLLVGDPVADNCCAEKICILPNRGLARTKVPIFLG
  IQGGSRCLACVETEEGPSLQLEDVNIEELYKGGEEATRFTFFQSSSGSAFRLEAAAWPGW
  FLCGPAEPQQPVQLTKESEPSARTKFYFEQSW
• Function: Cytokine with immunomodulatory activity. Alone, does not induce cytokine production, but reduces IL22 and IL17A production by T-cells in response to heat-killed Candida albicans. Reduces IL36G-induced production of IL8 by peripheral blood mononuclear cells. Increases IL6 production by dendritic cells stimulated by bacterial lipopolysaccharides (LPS). Ligand for IL-36R/IL1RL2.
• Tissue Specificity: Expressed in fetal skin, spleen and tonsil. Expressed mostly in the basal epithelia of skin and in proliferating B-cells of the tonsil.
• KEGG Pathway: Cytokine-cytokine receptor interaction (hsa04060)
• Reactome Pathway:
  Interleukin-36 pathway (R-HSA-9014826)
  Interleukin-38 signaling (R-HSA-9007892)

Molecular Interaction Atlas (MIA) of This DOT

31 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arthritis	DIST1YEL	Definitive	Biomarker	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Allergic asthma	DISHF0H3	Strong	Biomarker	[3]
Ankylosing spondylitis	DISRC6IR	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Asthma	DISW9QNS	Strong	Biomarker	[3]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
Autoimmune disease	DISORMTM	Strong	Biomarker	[6]
Colitis	DISAF7DD	Strong	Biomarker	[7]
Corneal neovascularization	DISKOGZP	Strong	Biomarker	[8]
Crohn disease	DIS2C5Q8	Strong	Biomarker	[9]
Dermatitis	DISY5SZC	Strong	Biomarker	[10]
Hidradenitis suppurativa	DIS3ZNAK	Strong	Altered Expression	[11]
Hyperlipidemia	DIS61J3S	Strong	Altered Expression	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[13]
Lung cancer	DISCM4YA	Strong	Biomarker	[14]
Myocardial infarction	DIS655KI	Strong	Biomarker	[15]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Obesity	DIS47Y1K	Strong	Biomarker	[16]
Psoriasis	DIS59VMN	Strong	Biomarker	[1]
Psoriatic arthritis	DISLWTG2	Strong	Biomarker	[1]
Pustular psoriasis	DISXOG13	Strong	Biomarker	[17]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[6]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[18]
Systemic sclerosis	DISF44L6	Strong	Biomarker	[19]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[20]
Retinopathy	DISB4B0F	moderate	Biomarker	[21]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[22]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Altered Expression	[6]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[23]
Neoplasm	DISZKGEW	Limited	Biomarker	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ivermectin	DMDBX5F	Approved	Ivermectin increases the expression of Interleukin-1 family member 10 (IL1F10).	[24]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Interleukin-1 family member 10 (IL1F10).	[25]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Interleukin-1 family member 10 (IL1F10).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Interleukin-1 family member 10 (IL1F10).	[28]

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 decreases the methylation of Interleukin-1 family member 10 (IL1F10).	[27]

References

• [1] IL-36, IL-37, and IL-38 Cytokines in Skin and Joint Inflammation: A Comprehensive Review of Their Therapeutic Potential.Int J Mol Sci. 2019 Mar 13;20(6):1257. doi: 10.3390/ijms20061257.
• [2] Interleukin-1 Family Cytokines: Keystones in Liver Inflammatory Diseases.Front Immunol. 2019 Aug 27;10:2014. doi: 10.3389/fimmu.2019.02014. eCollection 2019.
• [3] Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma.Cell Mol Immunol. 2020 Jun;17(6):631-646. doi: 10.1038/s41423-019-0300-7. Epub 2019 Oct 23.
• [4] The enigmatic role of IL-38 in inflammatory diseases.Cytokine Growth Factor Rev. 2018 Feb;39:26-35. doi: 10.1016/j.cytogfr.2018.01.001. Epub 2018 Jan 12.
• [5] Is Interleukin-38 a key player cytokine in atherosclerosis immune gene therapy?.Med Hypotheses. 2019 Apr;125:139-143. doi: 10.1016/j.mehy.2019.02.048. Epub 2019 Feb 28.
• [6] IL-38: A New Player in Inflammatory Autoimmune Disorders.Biomolecules. 2019 Aug 5;9(8):345. doi: 10.3390/biom9080345.
• [7] Distinct expression of interleukin (IL)-36, and , their antagonist IL-36Ra and IL-38 in psoriasis, rheumatoid arthritis and Crohn's disease.Clin Exp Immunol. 2016 May;184(2):159-73. doi: 10.1111/cei.12761. Epub 2016 Feb 22.
• [8] The Effect of Interleukin 38 on Inflammation-induced Corneal Neovascularization.Curr Mol Med. 2019;19(8):589-596. doi: 10.2174/1566524019666190627122655.
• [9] The novel interleukin-1 cytokine family members in inflammatory diseases.Curr Opin Rheumatol. 2017 Mar;29(2):208-213. doi: 10.1097/BOR.0000000000000361.
• [10] IL-38 Ameliorates Skin Inflammation and Limits IL-17 Production from T Cells.Cell Rep. 2019 Apr 16;27(3):835-846.e5. doi: 10.1016/j.celrep.2019.03.082.
• [11] Interleukin-36 in hidradenitis suppurativa: evidence for a distinctive proinflammatory role and a key factor in the development of an inflammatory loop.Br J Dermatol. 2018 Mar;178(3):761-767. doi: 10.1111/bjd.16019. Epub 2018 Jan 31.
• [12] Elevated Interleukin-38 Level Associates with Clinical Response to Atorvastatin in Patients with Hyperlipidemia.Cell Physiol Biochem. 2018;49(2):653-661. doi: 10.1159/000493029. Epub 2018 Aug 30.
• [13] Clinical implications of the novel cytokine IL-38 expressed in lung adenocarcinoma: Possible association with PD-L1 expression.PLoS One. 2017 Jul 20;12(7):e0181598. doi: 10.1371/journal.pone.0181598. eCollection 2017.
• [14] Reduced interleukin-38 in non-small cell lung cancer is associated with tumour progression.Open Biol. 2018 Oct 31;8(10):180132. doi: 10.1098/rsob.180132.
• [15] Interleukin-38 alleviates cardiac remodelling after myocardial infarction.J Cell Mol Med. 2020 Jan;24(1):371-384. doi: 10.1111/jcmm.14741. Epub 2019 Nov 20.
• [16] Hydrodynamic delivery of IL-38 gene alleviates obesity-induced inflammation and insulin resistance.Biochem Biophys Res Commun. 2019 Jan 1;508(1):198-202. doi: 10.1016/j.bbrc.2018.11.114. Epub 2018 Nov 23.
• [17] Differential Expression of IL-36 Family Members and IL-38 by Immune and Nonimmune Cells in Patients with Active Inflammatory Bowel Disease.Biomed Res Int. 2018 Dec 10;2018:5140691. doi: 10.1155/2018/5140691. eCollection 2018.
• [18] In vivo anti-inflammatory activities of novel cytokine IL-38 in Murphy Roths Large (MRL)/lpr mice.Immunobiology. 2017 Mar;222(3):483-493. doi: 10.1016/j.imbio.2016.10.012. Epub 2016 Oct 17.
• [19] The Roles of IL-1 Family Cytokines in the Pathogenesis of Systemic Sclerosis.Front Immunol. 2019 Sep 13;10:2025. doi: 10.3389/fimmu.2019.02025. eCollection 2019.
• [20] Interleukin-38 in colorectal cancer: a potential role in precision medicine.Cancer Immunol Immunother. 2020 Jan;69(1):69-79. doi: 10.1007/s00262-019-02440-7. Epub 2019 Nov 30.
• [21] The Effect of Interleukin 38 on Angiogenesis in a Model of Oxygen-induced Retinopathy.Sci Rep. 2017 Jun 5;7(1):2756. doi: 10.1038/s41598-017-03079-z.
• [22] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [23] Novel inflammatory cytokines (IL-36, 37, 38) in the aqueous humor from patients with chronic primary angle closure glaucoma.Int Immunopharmacol. 2019 Jun;71:164-168. doi: 10.1016/j.intimp.2019.03.016. Epub 2019 Mar 20.
• [24] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [25] Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014 Jun;139(2):328-37. doi: 10.1093/toxsci/kfu053. Epub 2014 Mar 27.
• [26] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [27] 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.
• [28] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.