General Information of the m6A Target Gene (ID: M6ATAR00529)
Target Name Interleukin-6 (IL-6)
Synonyms
IL-6; B-cell stimulatory factor 2; BSF-2; CTL differentiation factor; CDF; Hybridoma growth factor; Interferon beta-2; IFN-beta-2
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Gene Name IL-6
Chromosomal Location 7p15.3
Family IL-6 superfamily
Function
Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway (Probable). The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable); IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (Probable). In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity); Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability. Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF. Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance . 'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis (By similarity). Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity). Also acts as a myokine (Probable). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection. Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).
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Gene ID 3569
Uniprot ID
IL6_HUMAN
HGNC ID
HGNC:6018
Ensembl Gene ID
ENSG00000136244
KEGG ID
hsa:3569
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
IL-6 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
Browse Regulator
Browse Disease
Methyltransferase-like 14 (METTL14) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL14
Cell Line MDA-MB-231 Homo sapiens
Treatment: siMETTL14 MDA-MB-231 cells
Control: MDA-MB-231 cells
GSE81164
Regulation
logFC: 1.55E+00
p-value: 4.20E-30
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary Mettl14 gene knockout significantly reduced the inflammatory response of macrophages and the development of atherosclerotic plaques, Mettl14 plays a vital role in macrophage inflammation in atherosclerosis via the NF-Kappa-B/Interleukin-6 (IL-6) signaling pathway.
Target Regulation Up regulation
Responsed Disease Atherosclerosis ICD-11: BD40.Z
Pathway Response IL-17 signaling pathway hsa04657
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In-vivo Model Mettl14 heterozygous mice (Mettl14-/+) were established from C57/BL6 mice by Cyagen Biosciences, Inc. (Suzhou, Jiangsu, China), using CRISPR/Cas9-based targeting and homology-directed repair. C57/BL6 and APOE-/- mice were purchased from Beijing Vital River Laboratory Animal Technology (Beijing, China). Mettl14-/+APOE-/- mice were generated by breeding Mettl14-/+ mice with APOE-/- mice. Eight- to 10-week-old male APOE-/- (WT) mice and Mettl14-/+APOE-/- (KO) mice were fed a high-cholesterol diet (D12108C, Opensource diets) for 12 weeks. Then, the mice were euthanized for further analysis.
Methyltransferase-like 3 (METTL3) [WRITER]
Representative RNA-seq result indicating the expression of this target gene regulated by METTL3
Cell Line ARPE-19 cell line Homo sapiens
Treatment: shMETTL3 ARPE-19 cells
Control: shControl ARPE-19 cells
GSE202017
Regulation
logFC: -1.10E+00
p-value: 7.68E-04
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [2]
Response Summary METTL3 knockdown suppressed Interleukin-6 (IL-6), matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs.
Target Regulation Up regulation
Responsed Disease Rheumatoid arthritis ICD-11: FA20
Cell Process Inflammatory response
In-vitro Model FLS (Rat fibroblast synovial cell line)
In-vivo Model To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.
YTH domain-containing protein 2 (YTHDC2) [READER]
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [3]
Response Summary This modification recruits the m6A reader YTHDC2 and found that YTHDC2 is necessary for the escape of the IL-6 transcript. m6A modification is essential to confer SOX resistance to the Interleukin-6 (IL-6) mRNA. These results shed light on how the host cell has evolved to use RNA modifications to circumvent viral manipulation of RNA fate during KSHV infection Kaposi's sarcoma.
Responsed Disease Kaposi's sarcoma ICD-11: 2B57
In-vitro Model iSLK.219 Clear cell renal cell carcinoma Homo sapiens CVCL_B6YV
HEK293T Normal Homo sapiens CVCL_0063
HEK293 Normal Homo sapiens CVCL_0045
Kaposi's sarcoma [ICD-11: 2B57]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [3]
Response Summary This modification recruits the m6A reader YTHDC2 and found that YTHDC2 is necessary for the escape of the IL-6 transcript. m6A modification is essential to confer SOX resistance to the Interleukin-6 (IL-6) mRNA. These results shed light on how the host cell has evolved to use RNA modifications to circumvent viral manipulation of RNA fate during KSHV infection Kaposi's sarcoma.
Responsed Disease Kaposi's sarcoma [ICD-11: 2B57]
Target Regulator YTH domain-containing protein 2 (YTHDC2) READER
In-vitro Model iSLK.219 Clear cell renal cell carcinoma Homo sapiens CVCL_B6YV
HEK293T Normal Homo sapiens CVCL_0063
HEK293 Normal Homo sapiens CVCL_0045
Atherosclerosis [ICD-11: BD40]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary Mettl14 gene knockout significantly reduced the inflammatory response of macrophages and the development of atherosclerotic plaques, Mettl14 plays a vital role in macrophage inflammation in atherosclerosis via the NF-Kappa-B/Interleukin-6 (IL-6) signaling pathway.
Responsed Disease Atherosclerosis [ICD-11: BD40.Z]
Target Regulator Methyltransferase-like 14 (METTL14) WRITER
Target Regulation Up regulation
Pathway Response IL-17 signaling pathway hsa04657
In-vitro Model THP-1 Childhood acute monocytic leukemia Homo sapiens CVCL_0006
In-vivo Model Mettl14 heterozygous mice (Mettl14-/+) were established from C57/BL6 mice by Cyagen Biosciences, Inc. (Suzhou, Jiangsu, China), using CRISPR/Cas9-based targeting and homology-directed repair. C57/BL6 and APOE-/- mice were purchased from Beijing Vital River Laboratory Animal Technology (Beijing, China). Mettl14-/+APOE-/- mice were generated by breeding Mettl14-/+ mice with APOE-/- mice. Eight- to 10-week-old male APOE-/- (WT) mice and Mettl14-/+APOE-/- (KO) mice were fed a high-cholesterol diet (D12108C, Opensource diets) for 12 weeks. Then, the mice were euthanized for further analysis.
Rheumatoid arthritis [ICD-11: FA20]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [2]
Response Summary METTL3 knockdown suppressed Interleukin-6 (IL-6), matrix metalloproteinase (MMP)-3, and MMP-9 levels in human RA-FLSs and rat AIA-FLSs.
Responsed Disease Rheumatoid arthritis [ICD-11: FA20]
Target Regulator Methyltransferase-like 3 (METTL3) WRITER
Target Regulation Up regulation
Cell Process Inflammatory response
In-vitro Model FLS (Rat fibroblast synovial cell line)
In-vivo Model To establish the adjuvant-induced arthritis (AIA) model, the rats were given complete Freund's adjuvant (CFA; Chondrex, Inc.) on the left paw of 0.1 ml per 100 g of body weight. Additionally, the rats were injected with normal saline to create the negative control (NC) group.
References
Ref 1 Mettl14 mediates the inflammatory response of macrophages in atherosclerosis through the NF-KappaB/IL-6 signaling pathway. Cell Mol Life Sci. 2022 May 22;79(6):311. doi: 10.1007/s00018-022-04331-0.
Ref 2 METTL3 Promotes Activation and Inflammation of FLSs Through the NF-KappaB Signaling Pathway in Rheumatoid Arthritis. Front Med (Lausanne). 2021 Jul 6;8:607585. doi: 10.3389/fmed.2021.607585. eCollection 2021.
Ref 3 The m(6)A reader YTHDC2 is essential for escape from KSHV SOX-induced RNA decay. Proc Natl Acad Sci U S A. 2022 Feb 22;119(8):e2116662119. doi: 10.1073/pnas.2116662119.