InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-205938

interleukin 1 beta

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 21170027

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.

PMID 21228274

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.

PMID 21602824

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.

PMID 21270399

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.

PMID 21628463

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)

PMID 22426547

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)

PMID 24022484

Under acidic conditions both pro-inflammatory forms of Il1a and Il1b are regulated independently of the NLRP3 inflammasome.

PMID 24692555

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.

PMID 25422455

Actin polymerization is required for Nlrc4-dependent regulation of intracellular bacterial burden, inflammasome assembly, pyroptosis, and Il1b production.

PMID 25483963

Autophagy causes PELI3 degradation during Tlr4-signalling, subsequently inhibiting Il1b expression and impairing the hyperinflammatory phase during sepsis.

PMID 25689249

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.

PMID 25781937

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.

PMID 25683052

Mirlet7f and its target Tnfaip3 regulate immune responses to Mycobacterium tuberculosis and control bacterial burden by augmenting the production of Tnf and Il1b.

PMID 25595775

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.

PMID 26056255

Type 1 regulatory (Tr1) cells suppress Il1b transcription and Casp1 activation via an IL10R �??dependent mechanism.

PMID 26536497

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

PMID 20195505

[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.

PMID 20401526

[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.

PMID 20620944

[Homo sapiens] IL1B-producing conventional dendritic cells preserves and expands IL-22(+)AHR(+) immature human natural killer cells in the secondary lymphoid tissue.

PMID 21170027

[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)

PMID 21228274

[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.

PMID 21602824

[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)

PMID 21270399

[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)

PMID 21628463

[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.

PMID 22158745

[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.

PMID 22426547

[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.

PMID 24277153

[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.

PMID 24323452

[Homo sapiens] Protein-bound polysaccharide-K can activate the NLRP3 inflammasome and induce IL1B in a TLR2- and NLRP3-dependent manner.

PMID 25463072

[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.

PMID 25474109

[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.

PMID 25964352

[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

PMID 25637949

[Homo sapiens] DEFB103A and RNASE7 are induced in human umbilical endothelial cells (HUVECs) by classical inflammatory cytokines such as: IFNG, IL1B and TNF.

PMID 26032420

[Homo sapiens] Antibody-dependent enhancement (ADE) of Dengue virus serotype 2 (DENV-2) elevates mature IL1B secretion via SYK signalling pathway in primary monocytes.

PMID 26187413

[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.

PMID 26324708

[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

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	20 [view]
Protein-Protein	6 [view]
Protein-DNA	14 [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

ENSG00000125538

View Gene Order

ENSBTAG00000001321

Not yet available

Pathways

NETPATH

REACTOME

REACT_233584

Cytokine Signaling in Immune system pathway

REACT_230745

Immune System pathway

REACT_261687

Signaling by Interleukins pathway

REACT_198700

Interleukin-1 processing pathway

REACT_224208

Interleukin-1 signaling pathway

KEGG

mmu04060

Cytokine-cytokine receptor interaction pathway

mmu04940

Type I diabetes mellitus pathway

mmu05010

Alzheimer's disease pathway

mmu04640

Hematopoietic cell lineage pathway

mmu04620

Toll-like receptor signaling pathway pathway

mmu04010

MAPK signaling pathway pathway

mmu04210

Apoptosis pathway

mmu05332

Graft-versus-host disease pathway

mmu05020

Prion diseases pathway

mmu04621

NOD-like receptor signaling pathway pathway

mmu04623

Cytosolic DNA-sensing pathway pathway

mmu05140

Leishmaniasis pathway

mmu05146

Amoebiasis pathway

mmu04380

Osteoclast differentiation pathway

mmu05144

Malaria pathway

mmu05142

Chagas disease (American trypanosomiasis) pathway

mmu05143

African trypanosomiasis pathway

INOH

INOH website

IL-1 signaling pathway pathway

INOH website

JAK STAT pathway and regulation pathway

INOH website

GPCR signaling pathway

PID NCI

Pathway Predictions based on Human Orthology Data

NETPATH

NetPath_13

IL1 pathway

REACTOME

REACT_22442

Interleukin-1 signaling pathway

REACT_23950

Interleukin-1 processing pathway

REACT_75790

Cytokine Signaling in Immune system pathway

REACT_6900

Immune System pathway

REACT_22232

Signaling by Interleukins pathway

REACT_213612

Cytokine Signaling in Immune system pathway

REACT_213138

Immune System pathway

REACT_211401

Interleukin-1 processing pathway

REACT_207826

Interleukin-1 signaling pathway

REACT_206833

Signaling by Interleukins pathway

KEGG

hsa04640

Hematopoietic cell lineage pathway

hsa04210

Apoptosis pathway

hsa04010

MAPK signaling pathway pathway

hsa04060

Cytokine-cytokine receptor interaction pathway

hsa05010

Alzheimer's disease pathway

hsa04940

Type I diabetes mellitus pathway

hsa04620

Toll-like receptor signaling pathway pathway

hsa05332

Graft-versus-host disease pathway

hsa05020

Prion diseases pathway

hsa04621

NOD-like receptor signaling pathway pathway

hsa04623

Cytosolic DNA-sensing pathway pathway

hsa05140

Leishmaniasis pathway

hsa05146

Amoebiasis pathway

hsa05144

Malaria pathway

hsa05142

Chagas disease (American trypanosomiasis) pathway

hsa04380

Osteoclast differentiation pathway

hsa05143

African trypanosomiasis pathway

INOH

INOH website

IL-1 signaling pathway pathway

INOH website

JAK STAT pathway and regulation pathway

INOH website

GPCR signaling pathway

PID NCI

anthraxpathway

Cellular roles of Anthrax toxin

il1pathway

IL1-mediated signaling events

il27pathway

IL27-mediated signaling events

il12_2pathway

IL12-mediated signaling events

il23pathway

IL23-mediated signaling events

ifngpathway

IFN-gamma pathway

Cross-References

SwissProt

P10749

TrEMBL

Q3TI17

UniProt Splice Variant

Entrez Gene

16176

UniGene

Mm.222830

RefSeq

NM_008361 XM_006498795

OMIM

CCDS

CCDS16726

HPRD

IMGT

MGI ID

MGI:96543

MGI Symbol

Il1b

EMBL

AK168047 AY902319 BC011437 CH466519 M15131 X04964

GenPept

AAA39276 AAH11437 AAX90604 BAE40029 CAA28637 EDL28238

RNA Seq Atlas

16176