Mus musculus Gene: Il1b
Summary
InnateDB Gene IDBG-205936.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Il1b
Gene Name interleukin 1 beta
Synonyms Il-1b; IL-1beta;
Species Mus musculus
Ensembl Gene ENSMUSG00000027398
Encoded Proteins
interleukin 1 beta
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Il1b acts as a growth factor for neutrophil progenitors and as a survival factor for mature neutrophils. In the absence of Ikbkb, the Il1b production is enhanced and provides a compensatory mechanism for maintaining antibacterial defense when NFKB is inhibited.
Il1b secretion in macrophages is regulated by autophagy by two mechanisms; sequestering of pro-Il1b in autophagosome during TLR stimulation, and processing/secretion of Il1b in a Nlrp3- and TRIF-dependent manner.
Il1b secretion is induced only during viable E. coli infection (as oppose to heat-killed E. coli or LPS), viable bacteria specifically elicit cleavage of pro-Il1b.
Il1b derived from alveolar macrophages is the critical mediator which induces chemokine production in nonhematopoietic cells in the lung, resulting in swift and robust recruitment of infection-controlling neutrophils into the airways.
Il1b secretion is tightly regulated by the redox status in myeloid cells. TLR engagement in monocytes induces ROS generation followed by a sustained antioxidant response and efficient Il1b secretion. In macrophages, the antioxidant systems are in an upregulated state, and therefore buffers the TLR induction of the redox response, which results in low Il1b processing and secretion. (Demonstrated in human)
Il1b is an inflammatory cytokine that binds to its primary receptor, Il1r1, that then recruits the accessory protein Il1rap to form a signalling-competent heterotrimeric complex. (Demonstrated in human)
Under acidic conditions both pro-inflammatory forms of Il1a and Il1b are regulated independently of the NLRP3 inflammasome.
Group B streptococcus induces Il1b, and activates the NLRP3 inflammasome by a mechanism that requires hemolysin-mediated lysosomal leakage, which enhances the interaction of bacterial RNA with NLRP3.
Actin polymerization is required for Nlrc4-dependent regulation of intracellular bacterial burden, inflammasome assembly, pyroptosis, and Il1b production.
Autophagy causes PELI3 degradation during Tlr4-signalling, subsequently inhibiting Il1b expression and impairing the hyperinflammatory phase during sepsis.
Activation of the Nlrp3 inflammasome is detrimental during leishmaniasis. Mice lacking the inflammasome components Nlrp3, Pycard, Casp1 exhibit defective Il1b and Il18 production at the infection site and are resistant to cutaneous Leishmania major infection.
Escherichia coli toxin CNF1 promotes the maturation/secretion of Il1b while the α-hemolysin toxin inhibits Il1b secretion without affecting the recruitment of Ly6g+ cells.
Mirlet7f and its target Tnfaip3 regulate immune responses to Mycobacterium tuberculosis and control bacterial burden by augmenting the production of Tnf and Il1b.
Defb1 is important for the control of early mucosal Candida infection and plays a critical role in the induction of innate inflammatory mediators including, Il1b, Il6, Cxcl1, Il17a, and Il17f.
Type 1 regulatory (Tr1) cells suppress Il1b transcription and Casp1 activation via an IL10R ??dependent mechanism.
NLRP3 inflammasome formation is dispensable for alum-induced innate immunity but Il1a and Il1b are both necessary for alum-induced neutrophil influx in vivo.
InnateDB Annotation from Orthologs
Summary
[Homo sapiens] IL1B is an important proinflammatory cytokine that activates monocytes, macropages, and neutrophils. IL1B processing during infection is a complex process in which the inflammasomes are only one of several activation mechanisms.
[Homo sapiens] Mature IL1B production requires, in addition to the synthesis of pro-IL1B, cleavage of the precursor protein by the inflammatory CASP1 (Caspase-1) which is controlled within the NLRP3 inflammasome.
[Homo sapiens] IL1B-producing conventional dendritic cells preserves and expands IL-22(+)AHR(+) immature human natural killer cells in the secondary lymphoid tissue.
[Homo sapiens] IL1B acts as a growth factor for neutrophil progenitors and as a survival factor for mature neutrophils. In the absence of IKBKB, the IL1B production is enhanced and provides a compensatory mechanism for maintaining antibacterial defense when NFKB is inhibited. (Demonstrated in murine model)
[Homo sapiens] IL1B secretion in macrophages is regulated by autophagy by two mechanisms; sequestering of pro-IL1B in autophagosome during TLR stimulation, and processing,secretion of IL1B in a NLRP3- and TRIF-dependent manner.
[Homo sapiens] IL1B secretion is induced only during viable E. coli infection (as oppose to heat-killed E. coli or LPS); Viable bacteria specifically elicit cleavage of pro-IL1B. (Demonstrated in murine model)
[Homo sapiens] IL1B derived from alveolar macrophages is the critical mediator which induces chemokine production in non-hematopoietic cells in the lung, resulting in swift and robust recruitment of infection-controlling neutrophils into the airways. (Demonstrated in murine model)
[Homo sapiens] IL1B secretion is tightly regulated by the redox status in myeloid cells. TLR engagement in monocytes induces ROS generation followed by a sustained antioxidant response and efficient IL1B secretion. In macrophages, the antioxidant systems are in an upregulated state, and therefore buffers the TLR induction of the redox response, which results in low IL1B processing and secretion.
[Homo sapiens] IL1B is an important component of the cellular network involving macrophages and epithelial cells, which facilitates IL8 chemokine expression and aids neutrophil recruitment during pneumococcal pneumonia.
[Homo sapiens] IL1B is an inflammatory cytokine that binds to its primary receptor, IL1R1, that then recruits the accessory protein IL1RAP to form a signalling-competent heterotrimeric complex.
[Homo sapiens] TLR8 plays a pathogenic role in disease whereby its expression is increased in patients with systemic arthritis and is correlated with the elevation of IL1B levels and disease status.
[Homo sapiens] Protein-bound polysaccharide-K can activate the NLRP3 inflammasome and induce IL1B in a TLR2- and NLRP3-dependent manner.
[Homo sapiens] Interleukin-1 (IL1A/IL1B) plays a key role in the interaction between local vessel wall cells and invading monocytes to multiply cholesterol-triggered inflammation in the vessel wall.
[Homo sapiens] IFNG interferes with the IL-1/NFKBIZ axis in β-glucan-activated dendritic cells and promotes T cell-mediated immune responses with increased release of IFNG and IL22, and diminished production of IL17A.
[Homo sapiens] CASP4 is a critical regulator of noncanonical inflammasome activation that initiates defence against bacterial pathogens in primary macrophages by mediating cell death and IL1A release
[Homo sapiens] DEFB103A and RNASE7 are induced in human umbilical endothelial cells (HUVECs) by classical inflammatory cytokines such as: IFNG, IL1B and TNF.
[Homo sapiens] Antibody-dependent enhancement (ADE) of Dengue virus serotype 2 (DENV-2) elevates mature IL1B secretion via SYK signalling pathway in primary monocytes.
[Homo sapiens] Differentiation of Type 3 innate lymphoid cells (ILC3) to IL7R(+) ILC1 is reversible whereas IL7R(+) ILC1 can differentiate to ILC3 in the presence of IL2, IL23A, and IL1B dependent on the transcription factor RORC, and this process is enhanced in the presence of retinoic acid.
[Homo sapiens] 20-kDa IL1B generated from CASP1 cleaved pro-IL1B limits the available pro-IL1B for generation of CASP1 cleaved 17-kDa IL1B, thus reducing inflammation.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000125538:
The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE). This cytokine is an important mediator of the inflammatory response, and is involved in a variety of cellular activities, including cell proliferation, differentiation, and apoptosis. The induction of cyclooxygenase-2 (PTGS2/COX2) by this cytokine in the central nervous system (CNS) is found to contribute to inflammatory pain hypersensitivity. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. [provided by RefSeq, Jul 2008]
Gene Information
Type Protein coding
Genomic Location Chromosome 2:129364570-129371139
Strand Reverse strand
Band F1
Transcripts
ENSMUST00000028881 ENSMUSP00000028881
ENSMUST00000141979
ENSMUST00000155994
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 28 interaction(s) predicted by orthology.
Experimentally validated
Total 19 [view]
Protein-Protein 6 [view]
Protein-DNA 13 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 28 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005125 cytokine activity
GO:0005149 interleukin-1 receptor binding
GO:0019904 protein domain specific binding
Biological Process
GO:0000165 MAPK cascade
GO:0000187 activation of MAPK activity
GO:0001660 fever generation
GO:0001934 positive regulation of protein phosphorylation
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0008285 negative regulation of cell proliferation
GO:0009743 response to carbohydrate
GO:0010575 positive regulation vascular endothelial growth factor production
GO:0010628 positive regulation of gene expression
GO:0010829 negative regulation of glucose transport
GO:0019221 cytokine-mediated signaling pathway
GO:0030213 hyaluronan biosynthetic process
GO:0030593 neutrophil chemotaxis
GO:0030730 sequestering of triglyceride
GO:0031622 positive regulation of fever generation
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032308 positive regulation of prostaglandin secretion
GO:0032496 response to lipopolysaccharide
GO:0032611 interleukin-1 beta production
GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production
GO:0032729 positive regulation of interferon-gamma production
GO:0032755 positive regulation of interleukin-6 production
GO:0032757 positive regulation of interleukin-8 production
GO:0033198 response to ATP
GO:0034116 positive regulation of heterotypic cell-cell adhesion
GO:0035234 ectopic germ cell programmed cell death
GO:0035505 positive regulation of myosin light chain kinase activity
GO:0035690 cellular response to drug
GO:0042102 positive regulation of T cell proliferation
GO:0042346 positive regulation of NF-kappaB import into nucleus
GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043407 negative regulation of MAP kinase activity
GO:0043491 protein kinase B signaling
GO:0045080 positive regulation of chemokine biosynthetic process
GO:0045086 positive regulation of interleukin-2 biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045410 positive regulation of interleukin-6 biosynthetic process
GO:0045429 positive regulation of nitric oxide biosynthetic process
GO:0045766 positive regulation of angiogenesis
GO:0045833 negative regulation of lipid metabolic process
GO:0045840 positive regulation of mitosis
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046330 positive regulation of JNK cascade
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0050796 regulation of insulin secretion
GO:0050900 leukocyte migration
GO:0050995 negative regulation of lipid catabolic process
GO:0050996 positive regulation of lipid catabolic process
GO:0051044 positive regulation of membrane protein ectodomain proteolysis
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051781 positive regulation of cell division
GO:0060559 positive regulation of calcidiol 1-monooxygenase activity
GO:0070164 negative regulation of adiponectin secretion
GO:0070487 monocyte aggregation
GO:0071260 cellular response to mechanical stimulus
GO:0071310 cellular response to organic substance
GO:0071407 cellular response to organic cyclic compound
GO:0071639 positive regulation of monocyte chemotactic protein-1 production
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:2001240 negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Cellular Component
GO:0005615 extracellular space
GO:0030141 secretory granule
GO:0031982 vesicle
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Not yet available
Non-SSD Ortholog
Possible paralog/unusual divergence/ gene prediction error
Pathways
NETPATH
REACTOME
Cytokine Signaling in Immune system pathway
Immune System pathway
Signaling by Interleukins pathway
Interleukin-1 processing pathway
Interleukin-1 signaling pathway
KEGG
MAPK signaling pathway pathway
Cytokine-cytokine receptor interaction pathway
Apoptosis pathway
Osteoclast differentiation pathway
Toll-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hematopoietic cell lineage pathway
Type I diabetes mellitus pathway
Alzheimer's disease pathway
Prion diseases pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Malaria pathway
Amoebiasis pathway
Graft-versus-host disease pathway
INOH
GPCR signaling pathway
IL-1 signaling pathway pathway
JAK STAT pathway and regulation pathway
PID BIOCARTA
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
IL1 pathway
REACTOME
Cytokine Signaling in Immune system pathway
Interleukin-1 processing pathway
Immune System pathway
Signaling by Interleukins pathway
Interleukin-1 signaling pathway
Cytokine Signaling in Immune system pathway
Immune System pathway
Interleukin-1 processing pathway
Interleukin-1 signaling pathway
Signaling by Interleukins pathway
KEGG
MAPK signaling pathway pathway
Cytokine-cytokine receptor interaction pathway
Apoptosis pathway
Osteoclast differentiation pathway
Toll-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hematopoietic cell lineage pathway
Type I diabetes mellitus pathway
Alzheimer's disease pathway
Prion diseases pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Malaria pathway
Amoebiasis pathway
Graft-versus-host disease pathway
INOH
GPCR signaling pathway
IL-1 signaling pathway pathway
JAK STAT pathway and regulation pathway
PID BIOCARTA
Signal transduction through il1r [Biocarta view]
Nfkb activation by nontypeable hemophilus influenzae [Biocarta view]
PID NCI
Cellular roles of Anthrax toxin
IL1-mediated signaling events
IL27-mediated signaling events
IL12-mediated signaling events
IL23-mediated signaling events
IFN-gamma pathway
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Mm.222830
RefSeq NM_008361 XM_006498795
OMIM
CCDS CCDS16726
HPRD
IMGT
MGI ID
MGI Symbol
EMBL
GenPept
RNA Seq Atlas