Molecule Information

General Information of the Molecule (ID: Mol00436)

• Name: Interleukin-1 beta (IL1B) ,Homo sapiens
• Synonyms: IL-1 beta; Catabolin; IL1F2
• Molecule Type: Protein
• Gene Name: IL1B
• Gene ID: 3553
• Location: chr2:112829751-112836816[-]
• Sequence:
  MAEVPELASEMMAYYSGNEDDLFFEADGPKQMKCSFQDLDLCPLDGGIQLRISDHHYSKG
  FRQAASVVVAMDKLRKMLVPCPQTFQENDLSTFFPFIFEEEPIFFDTWDNEAYVHDAPVR
  SLNCTLRDSQQKSLVMSGPYELKALHLQGQDMEQQVVFSMSFVQGEESNDKIPVALGLKE
  KNLYLSCVLKDDKPTLQLESVDPKNYPKKKMEKRFVFNKIEINNKLEFESAQFPNWYIST
  SQAENMPVFLGGTKGGQDITDFTMQFVSS
• 3D-structure: PDB ID: 5MVZ; Classification: Signaling protein; Method: X-ray diffraction; Resolution: 2.15 Å
• Function: Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells. Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6. Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore.
• Uniprot ID: IL1B_HUMAN
• Ensembl ID: ENSG00000125538
• HGNC ID: HGNC:5992

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  RTDM: Regulation by the Disease Microenvironment

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Disease Class: Bladder cancer [ICD-11: 2C94.0] [1]

• Resistant Disease: Bladder cancer [ICD-11: 2C94.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Bladder cancer [ICD-11: 2C94]
• The Specified Disease: Bladder cancer
• The Studied Tissue: Bladder tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.39E-07; Fold-change: 2.53E-01; Z-score: 8.80E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• In Vitro Model: UM-UC-3 cells; Bladder; Homo sapiens (Human); CVCL_1783
• In Vivo Model: Balb/cA Jcl nu/nu nude mice xenografts model; Mus musculus
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: Cell count assay
• Mechanism Description: Aldo-keto reductase 1C1 (AkR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. Antagonized AkR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. Metastatic tumor cells possess higher expression levels of endogenous IL-6 and IL-1beta and their receptors. IL-1beta enhanced the expression of AkR1C1 in the three bladder cancer cell lines, UM-UC-3, TCC-SUP, and 5637 cells. Inhibition of 17beta-estradiol by AkR1C1 may recover cell motility in cancer cells.

Brinzolamide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Asthma [ICD-11: CA23.0] [2]

• Resistant Disease: Asthma [ICD-11: CA23.0]
• Resistant Drug: Brinzolamide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549/NF-kappaB-luc reporter cells; Lung; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: NF-kappaB activity assay
• Mechanism Description: Corticosteroid resistance causes significant morbidity in asthma, and drug repurposing may identify timely and cost-effective adjunctive treatments for corticosteroid resistance. gamma-linolenic acid, brinzolamide, and INCA-6 significantly reduced IL-1beta induced luciferase activity and potentiated the anti-inflammatory effect of dexamethasone in A549/NF-kappaB-luc reporter cells. These results demonstrate how existing drugs, including gamma-linolenic acid, brinzolamide, and INCA-6, may be repurposed to improve corticosteroid response in asthmatics.

MPA

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Corona Virus Disease 2019 [ICD-11: 1D92.0] [3]

• Sensitive Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Sensitive Drug: MPA
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: SARS coronaviruses have been shown to trigger the inflammasome and the release of interleukin-1beta (IL-1beta).Canakinumab is an IL-1beta antibody that neutralises the activity of IL-1beta.

Clinical Trial Drug(s) 1 drug(s) in total

Pristinamycin I

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Corona Virus Disease 2019 [ICD-11: 1D92.0] [4]

• Sensitive Disease: Corona Virus Disease 2019 [ICD-11: 1D92.0]
• Sensitive Drug: Pristinamycin I
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Bladder cancer [ICD-11: 2C94]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Bladder tissue
• The Specified Disease: Bladder cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.39E-07; Fold-change: 1.13E+00; Z-score: 3.57E+00

ICD Disease Classification 12

Asthma [ICD-11: CA23]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nasal and bronchial airway
• The Specified Disease: Asthma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.90E-02; Fold-change: 2.61E-01; Z-score: 2.32E-01

References

• Ref 1: Aldo-keto reductase 1C1 induced by interleukin-1Beta mediates the invasive potential and drug resistance of metastatic bladder cancer cells. Sci Rep. 2016 Oct 4;6:34625. doi: 10.1038/srep34625.
• Ref 2: Drug Repurposing to Treat Glucocorticoid Resistance in Asthma .J Pers Med. 2021 Mar 3;11(3):175. doi: 10.3390/jpm11030175. 10.3390/jpm11030175
• Ref 3: Canakinumab as treatment for COVID-19-related pneumonia: A prospective case-control study Int J Infect Dis. 2021 Mar;104:433-440. doi: 10.1016/j.ijid.2020.12.073. Epub 2020 Dec 29.
• Ref 4: Anakinra for severe forms of COVID-19: a cohort study Lancet Rheumatol. 2020 Jul;2(7):e393-e400. doi: 10.1016/S2665-9913(20)30164-8. Epub 2020 May 29.