◀ Back to TNF
ADAM17 — TNF
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
TNF
→
ADAM17
(directlyIncreases, TNF Activity)
Evidence: Pro-TNF-{alpha} is finally converted to active TNF-{alpha} by a membrane-bound metalloproteinase called TNF-{alpha} converting enzyme (TACE), although other matrix metalloproteinases also have a greater or lesser degree of TNF-{alpha} converting potential (Gearing et al., 1994Go). In vitro MMP-12 also releases active TNF-{alpha} from a synthetic pro-form,
-
NCI Pathway Database TNF receptor signaling pathway :
TNF-alpha complex (TNF)
→
TACE (ADAM17)
(modification, collaborate)
Black et al., Nature 1997*
Evidence: mutant phenotype, assay
-
NCI Pathway Database TNF receptor signaling pathway :
TACE (ADAM17)
→
sTNF-alpha complex (TNF)
(modification, activates)
Black et al., Nature 1997*
Evidence: mutant phenotype, assay
-
Reactome Reaction:
ADAM17
→
TNF
(reaction)
Robertshaw et al., Br J Anaesth 2005*, Moreira-Tabaka et al., PloS one 2012*
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Schlomann et al., J Neurosci 2000
(Heredodegenerative Disorders, Nervous System) :
In primary astrocytes from wild-type and WR mice, in primary cerebellar neurons, and in mouse motoneuron-like NSC19 cells,
ADAM8 expression was
induced up to 15-fold by mouse
TNF-alpha , in a dose dependent manner ... In both cell types,
ADAM8 was also
induced by human
TNF-alpha , indicating that TNF receptor type I ( p55 ) is involved
Hansen et al., J Immunol 2000
(Lymphoma) :
Hence,
TACE does not only
control the release of
TNF-alpha , but also that of sCD30
Hurtado et al., Neuropharmacology 2001
(Brain Ischemia) :
TACE enzymatic activity from OGD exposed slices was significantly inhibited by cycloheximide, suggesting that de novo synthesis of
TACE contributes to
TNF-alpha release after ischaemia ... Taken together, these data demonstrate that ( 1 )
TACE/ADAM17 activity accounts for the majority of TNF-alpha shedding after OGD in rat forebrain slices, ( 2 ) an increase in TACE expression
contributes , at least in part, to the rise in
TNF-alpha after OGD and ( 3 ) iNOS expression in OGD subjected brain slices results from TACE activity and subsequent increase in TNF-alpha levels
Ohta et al., J Rheumatol 2001
(Arthritis, Rheumatoid...) :
Expression and function of tumor necrosis factor-alpha (TNF-alpha) converting enzyme ( TACE ) in synovia of patients with rheumatoid arthritis ( RA ) were examined to investigate posttranslational
regulation of
TNF-alpha production by
TACE in RA ... A synthetic
TACE inhibitor significantly
reduced the release of
TNF-alpha and p75 TNF receptor from RA ST cells
Kottirsch et al., J Med Chem 2002
:
The best compound inhibits MMPs and
TACE with nanomolar potency and
inhibits the release of
TNFalpha from cells with an IC50 of 48 nM
Lee et al., Protein Sci 2002
:
Tumor necrosis factor-alpha
(TNF-alpha) converting enzyme ( TACE/ADAM-17 ) is
responsible for the release of
TNF-alpha , a potent proinflammatory cytokine associated with many chronic debilitating diseases such as rheumatoid arthritis
Wang et al., J Biol Chem 2003
:
Histamine induced shedding is blocked by
TNF-alpha protease inhibitor, an
inhibitor of
TNF-alpha converting enzyme , and through the H1 receptor via a MEK-1/p42 and p44 mitogen activated protein kinase pathway
Li et al., J Huazhong Univ Sci Technolog Med Sci 2002
:
In order to investigate the effects of LPS on the
TACE gene transcription and expression and its regulating
effect on the
TM-TNF secretion, in vitro studies were carried out on HL-60 cells stimulated by LPS
Wang et al., J Huazhong Univ Sci Technolog Med Sci 2003
(Inflammation) :
It was concluded that all the three types of TACE inhibitors can regulate the expression of
TACE at different levels and
inhibit sTNF alpha secretion, indicating TACE is a novel target for inflammation therapy
Meli et al., J Neuroimmunol 2004
(Disease Models, Animal...) :
We investigated the pharmacokinetics and the effect of
TNF484 , a water-soluble hydroxamate based
inhibitor of MMP and
TACE , on disease parameters and brain damage in a neonatal rat model of pneumococcal meningitis
Bzowska et al., Eur J Biochem 2004
:
Therefore,
ADAM17 dependent depletion of membrane bound
tumor necrosis factor receptors from endothelial cells might constitute a mechanism of self-protection in states of prolonged immunostimulation
Satoh et al., Eur J Heart Fail 2004
(Heart Failure) :
These observations suggest that TACE in PBMC is an important regulator of TNF-alpha maturation, meaning that
TACE may be a potential
target for the inhibition of cellular
TNF-alpha production in CHF
Shimoda et al., Clin Sci (Lond) 2005
(Arrhythmias, Cardiac...) :
To investigate the clinical significance of the TACE-TNF-alpha system in AMI, we examined
TACE mediated
TNF-alpha synthesis in PBMCs ( peripheral blood mononuclear cells ), which are a possible source of TNF-alpha in AMI ...
TACE mediated
TNF-alpha production was evaluated in cultured PBMCs with PMA, which is known to activate TACE ... These results demonstrate that TACE mediated TNF-alpha maturation in PBMCs may play an important role in poor outcomes from AMI, suggesting that
TACE may be a potential
target for the inhibition of cellular
TNF-alpha production in AMI
Pradillo et al., J Cereb Blood Flow Metab 2005
(Brain Ischemia) :
In summary, these data show that IPC produces neuronal upregulation of
TACE and TNFR1, and that the pathway
TACE/TNF-alpha/TNFR1/NF-kappaB is
involved in IT
Kresse et al., J Immunol 2005
(Drug-Induced Liver Injury...) :
Melphalan increased membrane bound but not secreted
TNF in Kupffer cells and
inhibited recombinant
TNF-alpha converting enzyme in vitro
Jarry et al., Br J Pharmacol 2006
(Colitis, Ischemic) :
Human colonic myocytes are involved in postischemic inflammation through
ADAM17 dependent
TNFalpha production
Federici et al., J Clin Invest 2005
(Diabetes Mellitus...) :
Unchecked
TACE activity
causes an increase in levels of soluble
TNF-alpha , which subsequently promotes diabetes and vascular inflammation
Malemud et al., Frontiers in bioscience : a journal and virtual library 2006
(Arthritis...) :
Adamlysins are membrane bound MMPs that also degrade aggrecan, but more importantly, one ADAM family member ( i.e.ADAM-17 ) is a tumor necrosis factor-alpha
(TNF-alpha) converting enzyme ( TACE ) that
activates pro-TNF-alpha
Zhan et al., J Cell Sci 2007
(Mechanotransduction, Cellular) :
In addition, conditioned medium from stretched myoblast cultures activated p38 in unstretched myoblasts, which
required TACE activity in the donor myoblasts, and
TNF-alpha receptors in the recipient myoblasts
Tellier et al., J Cell Physiol 2008
:
HDLs reduced the cholesterol and proteins ( including ADAM17 ) content of lipid rafts and triggered the
ADAM17 dependent cleavage of
TNF in the non-raft region of the membrane
Canault et al., Am J Pathol 2007
(Atherosclerosis) :
We sought to examine whether
TACE/ADAM17 is present on human plaque MPs and whether these MPs would
affect TNF and TNFR-1 cellular shedding
Charbonneau et al., J Biol Chem 2007
(Anoxia...) :
Hypoxia-inducible factor mediates hypoxic and
tumor necrosis factor alpha
induced increases in tumor necrosis factor-alpha converting
enzyme/ADAM17 expression by synovial cells
Rousseau et al., J Cell Sci 2008
(MAP Kinase Signaling System) :
Therefore, although
TACE activity per se is not
required for the LPS stimulated cell surface expression of
pre-TNF alpha , the phosphorylation of this protease might contribute to, or be required for, the cell surface expression of the pre-TNF alpha-TACE complex
Hiraoka et al., Biochem Biophys Res Commun 2008
:
A peptide cleavage assay in vitro showed that recombinant NRDc enhances the cleavage of
TNF-alpha induced by
TACE
Brennan et al., Eur J Immunol 2008
:
In the presence of IL-10,
TNF-alpha production and
activation of surface
TACE was significantly inhibited
Haga et al., Proc Natl Acad Sci U S A 2008
:
Modulation of
TNF-alpha converting enzyme by the spike protein of SARS-CoV and ACE2
induces TNF-alpha production and facilitates viral entry
Kim et al., J Neurosci 2008
(Alzheimer Disease...) :
Accordingly, it is possible that
TACE inhibitors could
reduce TNFalpha levels without increasing Abeta levels within the AD brain
Fréour et al., Int J Mol Med 2009
(Inflammatory Bowel Diseases) :
TNF-alpha production and the bioavailability of its receptors on the cell surface are
regulated by
TACE ( TNF-alpha converting enzyme ), a pleiotropic metalloprotease also known as ADAM17, and its specific inhibitor TIMP3
Mol et al., Toxicology 2009
(Blister) :
Since
TACE is
involved not only in degradation of cell-matrix adhesion structures, but also in ectodomain shedding of ligands for epidermal growth factor receptor (EGFR) and in release of
TNFalpha , these results imply TACE mediated pathways as a new concept in HD toxicity
Estrella et al., Am J Respir Cell Mol Biol 2009
(Rhinitis, Allergic, Perennial...) :
In contrast with the other HB-epidermal growth factor sheddases,
ADAM-10 and -17,
TNF-alpha in vitro
increased the expression of ADAM-12 by AEC, an effect amplified by IL-4 and IL-13
Cesaro et al., Am J Physiol Gastrointest Liver Physiol 2009
(Colitis...) :
TNF-alpha induced an early upregulation of
ADAM17 in T84 cells, whereas PMNL adhesion, H ( 2 ) O ( 2 ), or epithelial tight junction opening alone did not affect the amount of ADAM17
Nikolaidis et al., Shock 2010
:
Ron receptor tyrosine kinase negatively
regulates TNFalpha production in alveolar macrophages by inhibiting NF-kappaB activity and
Adam17 production
Sisto et al., Int Immunol 2009
(Sjogren's Syndrome) :
Our study demonstrated a dose dependent increase of TACE messenger RNA ( mRNA ) expression in anti-Ro/SSA Abs treated SGEC, followed by internalization, pro-domain shedding and activation of TACE protein, suggesting that increased
TACE activity is
necessary for the release of
TNF-alpha observed in anti-Ro/SSA Abs stimulated SGEC
Sisto et al., Immunobiology 2010
(Autoimmune Diseases...) :
Anti-Ro/SSA autoAbs determines TACE pro-domain shedding suggesting that
TACE activity is
necessary for the release of
TNF-a observed in anti-Ro/SSA autoAbs stimulated cells
Adrain et al., Science 2012
:
Tumor necrosis factor signaling
requires iRhom2 to promote trafficking and activation of
TACE
Dreymueller et al., EMBO Mol Med 2012
(Inflammation...) :
Induced vascular permeability, oedema formation, release of
TNF-a and IL-6 and pulmonary leukocyte recruitment were all markedly
reduced by GW280264X or endothelial
adam17-knockout
Perna et al., J Cell Biochem 2013
(Inflammation) :
Hydrogen sulfide reduces cell adhesion and relevant inflammatory triggering by preventing
ADAM17 dependent
TNF-a activation
Waheed et al., Mol Biol Cell 2013
:
Central role of the exchange factor GEF-H1 in
TNF-a induced sequential
activation of Rac,
ADAM17/TACE , and RhoA in tubular epithelial cells
McMahan et al., Am J Physiol Gastrointest Liver Physiol 2013
(Inflammation) :
We conclude that
ADAM17 regulates
TNF , TNFR1, and AR in the liver, and its expression in both hepatocytes and myeloid cells is important for TNF regulation after LPS injury or 2/3 PH, but is not required for liver regeneration
Fiorucci et al., Aliment Pharmacol Ther 1998
:
TACE inhibitors
prevent TNFalpha release and protect against TNFalpha mediated disease ... Agents that prevent TNFalpha mRNA transcription, e.g. lisophylline, PGE2, interleukin-10 and 8-BrcAMP, or
TACE inhibitors, e.g. EDTA, TAPI-2 and BB-3103,
inhibit TNFalpha release and protect rats against gastric mucosal injury induced by oral administration of aspirin