IL6

This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Interleukin 6

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 (PubMed:17075861, PubMed:12794819).
Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF (PubMed:12794819).
Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (PubMed:20823453).
'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 (PubMed:15124018).
Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).

Acute-phase responseManual Assertion Based On ExperimentTAS:BHF-UCL
Cellular response to hydrogen peroxideManual Assertion Based On ExperimentIDA:BHF-UCL
Cellular response to lipopolysaccharideManual Assertion Based On ExperimentIMP:MGI
Cellular response to virusISS:UniProtKB
Cytokine-mediated signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Defense response to Gram-negative bacteriumManual Assertion Based On ExperimentTAS:BHF-UCL
Defense response to Gram-positive bacteriumManual Assertion Based On ExperimentTAS:BHF-UCL
Defense response to virusManual Assertion Based On ExperimentIDA:BHF-UCL
Endocrine pancreas developmentISS:BHF-UCL
Germinal center B cell differentiationISS:UniProtKB
Glucagon secretionISS:BHF-UCL
Glucose homeostasisManual Assertion Based On ExperimentIDA:UniProtKB
Hepatic immune responseManual Assertion Based On ExperimentIDA:BHF-UCL
Hepatocyte proliferationISS:UniProtKB
Humoral immune response1 PublicationIC:BHF-UCL
Inflammatory responseManual Assertion Based On ExperimentIDA:BHF-UCL
Interleukin-6-mediated signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Liver regenerationISS:UniProtKB
Maintenance of blood-brain barrierManual Assertion Based On ExperimentTAS:ARUK-UCL
Monocyte chemotaxis1 PublicationIC:BHF-UCL
Negative regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Negative regulation of bone resorptionISS:BHF-UCL
Negative regulation of cell population proliferationManual Assertion Based On ExperimentTAS:ProtInc
Negative regulation of chemokine productionISS:UniProtKB
Negative regulation of collagen biosynthetic processManual Assertion Based On ExperimentIDA:BHF-UCL
Negative regulation of fat cell differentiation1 PublicationNAS:BHF-UCL
Negative regulation of interleukin-1-mediated signaling pathwayISS:BHF-UCL
Negative regulation of lipid storage1 PublicationNAS:BHF-UCL
Negative regulation of neurogenesisManual Assertion Based On ExperimentTAS:ARUK-UCL
Negative regulation of primary miRNA processingManual Assertion Based On ExperimentIGI:ARUK-UCL
Neuron cellular homeostasisManual Assertion Based On ExperimentTAS:ARUK-UCL
Neuron projection developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Neutrophil apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Neutrophil mediated immunityManual Assertion Based On ExperimentTAS:BHF-UCL
Platelet activationManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of acute inflammatory responseManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of apoptotic DNA fragmentationManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of apoptotic processManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of B cell activationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of chemokine productionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of cytokine production involved in inflammatory responseManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of epithelial to mesenchymal transitionManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of extracellular matrix disassemblyManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of gene expressionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of glial cell proliferationManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of immunoglobulin productionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of interleukin-1 beta productionManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of interleukin-10 productionManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of interleukin-17 productionBy SimilarityISS:ARUK-UCL
Positive regulation of interleukin-21 productionISS:UniProtKB
Positive regulation of interleukin-6 productionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of leukocyte adhesion to vascular endothelial cellManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of leukocyte chemotaxisManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of MAPK cascadeManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of neuroinflammatory responseManual Assertion Based On ExperimentTAS:ARUK-UCL
Positive regulation of osteoblast differentiationManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of peptidyl-serine phosphorylationManual Assertion Based On ExperimentIDA:MGI
Positive regulation of peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:MGI
Positive regulation of platelet aggregationManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of production of miRNAs involved in gene silencing by miRNAManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of receptor signaling pathway via JAK-STATManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of receptor signaling pathway via STATManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of smooth muscle cell proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of T cell proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of T-helper 2 cell cytokine productionISS:BHF-UCL
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of translationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIDA:ARUK-UCL
Positive regulation of type B pancreatic cell apoptotic processManual Assertion Based On ExperimentTAS:BHF-UCL
Positive regulation of tyrosine phosphorylation of STAT proteinManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of vascular endothelial growth factor productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Regulation of angiogenesis1 PublicationIC:BHF-UCL
Regulation of astrocyte activationManual Assertion Based On ExperimentTAS:ARUK-UCL
Regulation of glucagon secretionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of insulin secretionManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of microglial cell activationManual Assertion Based On ExperimentTAS:ARUK-UCL
Regulation of neuroinflammatory responseManual Assertion Based On ExperimentTAS:ARUK-UCL
Regulation of vascular endothelial growth factor productionManual Assertion Based On ExperimentIDA:BHF-UCL
Response to activityISS:UniProtKB
Response to glucocorticoidManual Assertion Based On ExperimentIDA:BHF-UCL
Response to peptidoglycan1 PublicationNAS:BHF-UCL
T follicular helper cell differentiationISS:UniProtKB
T-helper 17 cell lineage commitmentISS:UniProtKB
Vascular endothelial growth factor productionManual Assertion Based On ExperimentIDA:UniProtKB

Secreted

Rheumatoid arthritis systemic juvenile (RASJ):
An inflammatory articular disorder with systemic onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis.

N- and O-glycosylated.