◀ Back to TNF
FAS — TNF
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
FAS
→
TNF
(increases)
Evidence: incubation with TNF-alpha led to a 70% increase in Fas expression (Figure 5A and 5B, P < 0.001
-
NCI Pathway Database HIV-1 Nef: Negative effector of Fas and TNF-alpha:
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP/cIAP2/TRAF1/TRAF2/Ask1/RAIDD complex (TNFRSF1A-CASP2-TNF-FADD-TRADD-RIPK1-MAP3K5-TRAF1-TRAF2-BIRC3-CRADD)
→
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG complex (FASLG-CASP8-MAP3K5-FAS-DAXX-FADD)
(modification, activates)
Micheau et al., Cell 2003, Yang et al., Cell 1997, Saitoh et al., EMBO J 1998, Chang et al., Science 1998
-
NCI Pathway Database Caspase Cascade in Apoptosis:
sTNF-alpha/TNFR1A/TRADD/TRAF2/FADD complex (TNFRSF1A-TRADD-TRAF2-FADD-TNF)
→
FASLG/FAS (trimer)/FADD/FADD complex (FAS-FASLG-FADD)
(modification, activates)
Bodmer et al., Nat Cell Biol 2000, Sprick et al., Immunity 2000, Schneider-Brachert et al., Immunity 2004, Schneider-Brachert et al., J Clin Invest 2006, Lavrik et al., J Biol Chem 2008, Boldin et al., Cell 1996, Walczak et al., EMBO J 1997, Scaffidi et al., EMBO J 1998
Evidence: mutant phenotype, assay, physical interaction
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Otsuki et al., J Cell Physiol 1999
(Disease Models, Animal...) :
Apoptosis
induced by
TNF-alpha alone or with
CD95 ligation also occurred more frequently in null mouse HPC
Saile et al., Hepatology 1999
(Carbon Tetrachloride Poisoning) :
TGF-beta and
TNF-alpha significantly
reduced expression of
CD95L in activated HSCs, whereas CD95 expression remained unchanged
Ruemmele et al., J Cell Physiol 1999
:
Receptor studies showed that the
effect of
TNFalpha on
FAS was mediated via the p55 TNF receptor ... In colonic organ cultures, IFNgamma and
TNFalpha also
enhanced colonocyte
FAS expression, resulting in a markedly increased apoptotic response to stimulation of this receptor, as shown by in situ terminal deosyuridine triphosphate nick-end staining
Tsuboi et al., J Lab Clin Med 1999
(Arthritis, Rheumatoid) :
TNF-alpha augmented both
Fas expression and Fas mediated apoptosis more efficiently than did IL-1beta
Schelling et al., Kidney Int 1999
(Atrophy...) :
These data are supported by in vitro studies that showed that interleukin-1alpha or
tumor necrosis factor-alpha , cytokines that are secreted in chronic renal failure,
stimulated increases in
Fas expression in cultured RTCs
Luttmann et al., Scand J Immunol 2000
:
It has previously been shown that interferon-gamma (IFN-gamma) and
tumour necrosis factor-alpha (TNF-alpha) together
increase CD95 surface expression on eosinophils ... We therefore investigated whether the increase in
CD95 expression
mediated by
IFN-gamma/TNF-alpha indeed translates into increased, FasL mediated apoptosis of eosinophils ... This increase in CD95/FasL mediated apoptosis was correlated with an
IFN-gamma/TNF-alpha mediated increase in
CD95 expression
Ohshima et al., Cytokine 2000
(Arthritis, Rheumatoid...) :
Moreover, removal of
TNF-alpha activity by a neutralizing anti-TNF-alpha antibody ( cA2 )
restored Fas-ACD ... These results suggest the following : ( 1 )
Fas-ACD might be
diminished in vivo by local excessive
TNF-alpha and this might contribute in part to RASH
Matsumura et al., Clin Exp Rheumatol 2000
(Lymphadenitis...) :
Our findings suggest that IFN-gamma or
TNF-alpha secreted by infiltrating lymphocytes
induces ductal
Fas expression and ductal apoptosis in sialoadenitis associated with SS
Urayama et al., J Lab Clin Med 2000
:
The addition of vitamin K2 to the culture resulted in a dose dependent inhibition of functional
Fas expression on osteoblasts, in the
presence or absence of
TNF-alpha
Saile et al., Eur J Cell Biol 2001
:
TGF-beta as well as
TNF-alpha reduced spontaneous apoptosis and
CD95L expression ... We conclude that TGF-beta as well as
TNF-alpha may
act as surviving factors for activated rat HSC not only through reduction of
CD95L gene expression but also by upregulating the anti-apoptotic factors NFKB, bcl-xL and p21WAF1 and by downregulating the proapoptotic factor p53
Aschkenazi et al., Biol Reprod 2002
:
IFN-gamma and
TNFalpha promote
Fas expression and sensitivity, whereas IL-6 and IL-10 increase the resistance of trophoblast cells to Fas mediated apoptosis
Matsuki et al., Cell Death Differ 2002
(Hemorrhage...) :
Soluble Fas gene therapy protects against Fas mediated apoptosis of hepatocytes but not the lethal effects of
Fas induced
TNF-alpha production by Kupffer cells
Jo et al., Nephron 2002
:
Fas mRNA expression ( ratio of Fas/L-19 )
increased in the
TNF-alpha 5, 30 ng/ml and LPS treated group ( p < 0.01, p < 0.01, p = 0.02 ), but there was no difference between the low- and high-dose TNF-alpha groups
Kimura et al., Cell Death Differ 2002
(Carcinoma...) :
IkappaBalpha super repressor expression blocked the increase of whole cell and cell surface
FAS expression
induced by
TNF-alpha , but did not effect induction of FAS expression and cell surface FAS expression that resulted from irradiation
Kitaura et al., J Immunol 2002
:
Apoptosis of the adherent cells was markedly inhibited by anti-Fas ligand (FasL) Ab. RT-PCR and FACS analyses revealed that
TNF-alpha up-regulated
Fas transcription to lead to Fas expression on the surfaces of the adherent cells, whereas IL-12 could not induce Fas on the cells ... These results implied that apoptosis of the adherent cells in bone marrow cells might be caused by interaction between
TNF-alpha induced
Fas on the adherent cells and IL-12 induced FasL on the nonadherent cells
Sindhi et al., J Immunol Methods 2003
:
PD analyses suggested that in NHS samples containing CsA+SRL ( n=5 ), ( 1 ) PMA-Ionomycin stimulated T-cell expression of intracellular IL-2,
TNF-alpha , and IFN-gamma was inhibited by CsA, and minimally by SRL, and ( 2 ) the two agents
inhibited pokeweed mitogen ( PWM ) -stimulated B-cell expression of CD54 and
CD95 , but not CD86 ( ICAM-1, Fas antigen, and B7.2 ), synergistically
Ma et al., Zhongguo Shi Yan Xue Ye Xue Za Zhi 2002
:
Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) further
increased the
CD95 expression induced by positive cytokines
Ma et al., J Huazhong Univ Sci Technolog Med Sci 2002
:
The combinations of cytokines such as SCF + FL could up-regulate the expression of
CD95 in vitro culture and
tumor necrosis factor-alpha (TNF-alpha) and interon-gamma ( IFN-gamma ) further
increased the CD95 expression induced by positive cytokines
Yu et al., Urol Int 2003
(Carcinoma, Transitional Cell...) :
Synergism of
Fas mediated apoptosis and
tumor necrosis factor on adriamycin cytotoxicity to transitional cell carcinoma ... The synergism efficacy of
Fas mediated apoptosis and
TNF-alpha on adriamycin cytotoxicity of TCC cells was analyzed
Kimura et al., Cell Death Differ 2003
(Carcinoma...) :
On the other hand,
Fas expression was strongly
enhanced by
TNF/IFN-alpha , and inhibition of TNF/IFN-alpha induced NF-kappaB activation, by using NF-kappaB decoy, decreased Fas expression
Malewicz et al., J Biol Chem 2003
:
In addition, NF kappa B downstream of TNFR was
required for up-regulation of
Fas expression by endogenous
TNF secreted in response to TCR stimulation
Watanabe et al., Clin Immunol 2003
(Chronic Disease...) :
Fas ligand and
TNF-alpha were also
detected among pancreas infiltrating cells, whereas
Fas was rarely expressed in the pancreatic acinar cells
Thomas et al., Diabetes 2004
(Diabetes Mellitus, Type 1...) :
IL-1 action was not required for
induction of class I major histocompatibility complex or
Fas by
TNF and IFN-gamma
De Saint Jean et al., Exp Eye Res 2004
:
In the primary cultured cells,
TNFalpha induced an important upregulation of ICAM-1,
Fas and CD40 whereas CD44 and CD63 were significantly decreased
Filippatos et al., BMC cell biology 2004
:
Cultured human coronary artery endothelial cells ( HCAEC ) were exposed to the monoclonal
Fas activating antibody CH-11, to purified recombinant human Fas ligand, to the Fas neutralizing antibody ZB4, or to purified recombinant human
TNF-alpha
Welsh et al., Hematol J 2004
(Anemia, Aplastic) :
IFN-gamma/TNF-alpha induced upregulation of
CD95 on both normal and aplastic CD34+ cells, although the basal level of CD95 expression was increased in aplastic cells
Buntinx et al., J Neurosci Res 2004
:
In addition to direct cytotoxic effects, IFN-gamma and
TNF-alpha also
enhance the expression of
Fas , TNFR1, and MHC class I molecules in both cell lines
García-Moreno et al., Bone 2004
(Osteoporosis, Postmenopausal) :
TNFalpha increased the expression of Fas mRNA and cell surface
Fas expression
Chosa et al., Eur J Oral Sci 2004
(Adenocarcinoma...) :
These results suggest that the enhancement of the apoptosis caused by TNF-alpha resulted from increased sensitivity of the HSG cells to CH-11 mediated apoptosis due to
induction of
Fas protein by
TNF-alpha via the activation of NFkappaB
Zhou et al., Am J Physiol Gastrointest Liver Physiol 2004
(Intestinal Diseases) :
This difference in IL-10 KO mice was associated with an
increase in serum
tumor necrosis factor-alpha and interferon-gamma levels and with an increase in
Fas expression on fresh, isolated, small intestinal epithelial cells
Starace et al., FASEB J 2005
:
In the present paper, we have investigated the signal transduction mechanisms involved in the regulation of
Fas expression
induced by
TNF-alpha in mouse Sertoli cells ... Moreover, the use of the proteasome inhibitor lactacystin led us to demonstrate that NF-kappaB is required for
TNF-alpha mediated
Fas expression ... By using specific inhibitors for each MAPK, we confirmed the pivotal role of the IkappaB/NF-kappaB system by demonstrating that ERKs, p38, and JNK are not involved in
Fas up-regulation by
TNF-alpha
Sun et al., Mol Pharmacol 2005
:
This investigation further demonstrates that HR3 cells also exhibited cross-resistance to death ligands [
Fas inducing antibody and
tumor necrosis factor (TNF)-alpha ]
Krippner-Heidenreich et al., Mol Cell Biol 2005
:
We observed that this factor is rapidly translocated into the cell nucleus in response to various apoptotic stimuli, including activation of
Fas ,
stimulation by
tumor necrosis factor , and staurosporine and etoposide treatment
Li et al., Cancer Immunol Immunother 2006
(Neoplasms) :
The
TM-TNFalpha expressing tumors
up-regulated Fas ( CD95 ) expression and inhibited the expression of tumor metastasis associated molecule CD44v3
Carmona et al., J Immunol 2006
:
We additionally determined that IL-1beta and
TNF-alpha secretion by beta-glucan stimulated DCs was partially
regulated by
Fas-FasL
Chauhan et al., Anticancer Drugs 2007
:
The
Fas-Fas ligand interaction between macrophages and L929 cells increased the expression of Fas associated death domain, and
tumor necrosis factor-tumor necrosis factor receptor 1 interaction between macrophages and L929 cells
increased the expression of tumor necrosis factor receptor associated death domain in L929 cells
Krogerus et al., Transpl Immunol 2008
(Cytomegalovirus Infections) :
CMV enhanced development of CAN was associated with tubular apoptosis and concomitant increase of
TNF-alpha-TNF-R1 , rather than the
FAS-FAS-ligand activation
Guazzone et al., Microsc Res Tech 2009
(Inflammation...) :
Germ cells expressing TNFR1, IL-6R, and
Fas increase in number and undergo apoptosis, through the
TNF-alpha/TNFR1 , IL-6/IL-6R, and Fas/Fas L systems
Solarewicz-Madejek et al., Clin Exp Allergy 2009
(Asthma...) :
IFN-gamma and
TNF-alpha up-regulated TNFR1, TNFR2,
Fas and membrane FasL on SMC
Brodsky et al., J Hepatol 2009
(Disease Models, Animal...) :
AS101 inhibited
TNFalpha or
anti-FAS induced apoptotic processes in hepatocytes in vitro
Yoshimatsu et al., Bone 2009
:
We previously reported that IL-12 induces apoptosis in bone marrow cells treated with TNF-alpha in vitro via an interaction between
TNF-alpha induced
Fas and IL-12 induced Fas ligand (FasL), and that, as a result, osteoclastogenesis is inhibited ... These results suggest that IL-12 inhibits TNF-alpha mediated osteoclastogenesis and induces apoptotic changes through an interaction between
TNF-alpha induced
Fas and IL-12 induced FasL, in vivo, via a T cell independent mechanism
Bai-Feng et al., Diabetes Res Clin Pract 2010
:
The expression of iNOS and the promoting apoptosis gene Bax and
Fas were significantly
up-regulated by the induction of IL-1beta and
TNF-alpha
de Lima-Salgado et al., Cell Biochem Biophys 2011
:
Saturated
FAs were potent
inducers of
TNF-a expression and secretion under basal and inflammatory conditions ( in the presence of LPS )
Kitaura et al., Calcif Tissue Int 2011
:
We have reported that IL-12 and IL-18 induce apoptosis in bone marrow cells treated with TNF-a in vitro and that osteoclastogenesis is inhibited by the interaction of
TNF-a induced
Fas and the IL-12 induced Fas ligand (FasL)
Kageyama et al., Cardiovascular diabetology 2011
(Diabetes Mellitus, Experimental...) :
High glucose increased TNF-a production by HCAECs and exogenous
TNF-a up-regulated TNF-R1 and
Fas expression in HCAECs ... High glucose induced up-regulation of TNF-R1 and
Fas expression was undetectable in the
presence of
TNF-a
Schulze-Osthoff et al., EMBO J 1994
:
Whereas transcription factor NF-kappa B was readily activated by
TNF , activation was not
induced by triggering
APO-1/Fas
Aggarwal et al., FEBS Lett 1995
:
Whether
Fas , like
TNF receptor, also
mediates proliferation of normal human diploid fibroblasts ( HDF ), is not known ... The difference in the signaling was further evident from our observation that
TNF induced the expression of interleukin-6 but
anti-Fas did not
Nagafuji et al., Blood 1995
:
IFN-gamma and
TNF-alpha had a synergistic effect on the induction of
Fas , when both cytokines were added to the culture ... The
TNF-alpha induced
Fas expression is mediated by p55 TNF-alpha receptor ... These observations indicate that IFN-gamma and/or
TNF-alpha , well known as negative hematopoietic regulators,
induce functional
Fas on hematopoietic progenitor cells
Maciejewski et al., Br J Haematol 1995
(Anemia, Aplastic...) :
Interferon-gamma (IFN-gamma) and
tumour necrosis factor-alpha (TNF-alpha) , potent inhibitors of haemopoiesis,
enhance Fas receptor expression on bone marrow ( BM ) CD34+ cells, and both cytokines render haemopoietic progenitor cells susceptible to Fas mediated inhibition of colony formation due to the induction of apoptosis
Lens et al., J Immunol 1996
(Burkitt Lymphoma) :
In contrast to the strong effect of BCR ligation, APO-1 mAb induced apoptosis in only +/- 18 % of the Ramos cells after 48 h. Noticeably, addition of CD40 mAb or rTNF-alpha increased the percentage of cells ( +/- 46 % ) undergoing apoptosis, which correlated with an increase of
Fas/APO-1 membrane expression
induced by CD40 or
TNF-R ligation
Kohno et al., J Immunol 1996
(Leukemia, T-Cell) :
As
CD95 and TNF receptor are similar, and
TNF/TNF receptor binding
induces oxygen radicals, the involvement of oxidant and antioxidant systems in CD95 mediated apoptosis has been examined
Nagafuji et al., Nihon rinsho. Japanese journal of clinical medicine 1996
:
However, interferon-gamma(IFN-gamma) and/or
tumor necrosis factor-alpha (TNF-alpha) induced the expression of
Fas after 48 hours of serum-free culture ... The
TNF-alpha induced
Fas expression is mediated by p55-TNF-alpha receptor
Bárcena et al., Blood 1996
:
Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) further
increased the
CD95 expression induced by KL+GM-CSF
Nishimura et al., Blood 1997
(Graft vs Host Disease) :
Characterization of T-cell clones derived from peripheral blood lymphocytes of a patient with transfusion associated graft-versus-host disease :
Fas mediated killing by CD4+ and CD8+ cytotoxic T-cell clones and
tumor necrosis factor beta production by CD4+ T-cell clones
Nagafuji et al., Leukemia & lymphoma 1996
:
However, interferon-gamma (IFN-gamma) and/or
tumor necrosis factor-alpha (TNF-alpha) induced dose dependent expression of both Fas mRNA and
Fas protein on the surface of CD34+ cells after 48 hours of serum-free culture ...
TNF-alpha induced
Fas expression was mediated by p55-TNF-alpha receptor
Sato et al., Br J Haematol 1997
:
CD34+ cell
Fas-R expression was
increased by IFN-gamma and
TNF-alpha
Fukuo et al., Gerontology 1997
(Arteriosclerosis...) :
However, coincubation with NG-monomethyl-L-arginine, an inhibitor of nitric oxide ( NO ) synthesis, inhibited the upregulation of
Fas induced by IL-1 and
TNF-alpha
Dybedal et al., Blood 1997
:
In the presence of
TNF , activation of
Fas almost completely
blocked clonogenic growth of lineage depleted ( Lin- ) bone marrow ( BM ) progenitor cells in response to granulocyte-macrophage colony stimulating factor ( GM-CSF ), CSF-1, or a combination of multiple cytokines
Selleri et al., Br J Haematol 1997
:
Fas-receptor (Fas-R) expression can be
stimulated by IFN-gamma and
TNF-alpha
Meldrum et al., Am J Physiol 1998
(Myocardial Reperfusion Injury) :
TNF activation of TNF receptor 1 or
Fas may induce cardiac myocyte apoptosis
Schelling et al., Lab Invest 1998
(Kidney Failure, Chronic) :
These data are supported by in vitro studies showing that interleukin-1alpha and
tumor necrosis factor-alpha , cytokines secreted in chronic renal failure,
stimulated increases in
Fas expression in cultured RTC
Kawakami et al., J Lab Clin Med 1998
:
About 30 % of unstimulated PBLs expressed
Fas , and the expression was
augmented by interleukin-1beta (IL-1beta), IL-2,
tumor necrosis factor-alpha (TNF-alpha) , interferon-gamma (IFN-gamma), or PMA plus ionomycin
Choi et al., J Immunol 1999
:
Our data demonstrated that : 1 ) FasL is expressed constitutively on astrocytes taken from a fetus or an adult and that its expression increases when these cells are treated with IL-1, IL-6, or TNF-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more FasL ; 2 ) astrocytes induce apoptosis in MOLT-4 cells through FasL ; 3 )
Fas is also expressed constitutively and is
up-regulated by IL-1, IL-6, or
TNF-alpha in which the pretreatment of IFN-gamma triggers astrocytes to express more Fas ; 4 ) apoptosis occurs when fetal astrocytes are treated with agonistic anti-Fas IgM Ab after culture with IFN-gamma and TNF-alpha ; and 5 ) TNF related apoptosis inducing ligand is up-regulated in fetal astrocytes with stimuli of IL-1 or TNF-alpha