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CRP — IL6

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: CRP → IL6 (increases)
  Evidence: IL-6 stimulates liver production of c-reactive protein (CRP) and contributes to the elevated highly sensitive (hs)CRP levels in serum of obese subjects. 62,63
• OpenBEL Selventa BEL large corpus: CRP → IL6 (increases, IL6 Translocation)
  Evidence: Increased IL-6 enhances the release of acute phase proteins, including CRP, from the liver, enhancing inflammation further [30].
• WikiPathways Overview of nanoparticle effects: IL6 → CRP (unknown)

Protein-Protein interactions - manually collected from original source literature:

Studies that report less than 10 interactions are marked with *

• IRef Innatedb Interaction: IL6 — CRP (unknown, -) Street et al., J Endocrinol 2003*

Text-mined interactions from Literome

Cha-Molstad et al., J Immunol 2000 : Transcription of C-reactive protein (CRP) in Hep 3B cells is induced by IL-6 , acting through C/EBP isoforms and STAT3
Agrawal et al., J Immunol 2001 : Taken together, our findings indicate that binding of Rel p50 to the nonconsensus kappaB site enhances and stabilizes binding of C/EBPbeta to the CRP promoter and that binding of both C/EBPbeta and p50 to their overlapping cognate sites is required for induction of CRP expression by IL-6
Meier-Ewert et al., Clin Chem 2001 : CRP is synthesized by the liver in response to interleukin-6 , the serum concentration of which is subject to diurnal variation
Fernandez-Real et al., J Clin Endocrinol Metab 2001 (Insulin Resistance) : As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP) , we also controlled for the latter
Lindmark et al., JAMA 2001 (Angina, Unstable...) : Interleukin 6 (IL-6) induces C-reactive protein and fibrinogen, systemic markers of inflammation
Verma et al., Circulation 2002 (Arteriosclerosis...) : The effects of CRP on the secretion of ET-1 and IL-6 from HSVECs were also evaluated
Kleemann et al., Blood 2003 : CRP is predominantly expressed in hepatocytes and is induced by interleukin-1 (IL-1) and IL-6 under inflammatory situations, such as the acute phase
Baykal et al., Clin Rheumatol 2003 (Familial Mediterranean Fever) : In FMF patients IL-6 , TNF-alpha, sIL-2r, ESR, CRP and fibrinogen levels increased with the acute-phase reaction, especially in the attack period
Li et al., Coron Artery Dis 2003 : Simvastatin inhibits interleukin-6 release in human monocytes stimulated by C-reactive protein and lipopolysaccharide ... CRP and LPS induced the rapid release of IL-6 , with significantly elevated levels in cultured supernatants at 4 h in the CRP group and at 2 h in the LPS group ... The effects of CRP and LPS on IL-6 release of monocytes were dose and time dependent ... However, 10-8-10-6 mol/l simvastatin inhibited significantly the production of IL-6 in monocytes stimulated by CRP and LPS in a dose dependent manner, with the maximal inhibiting effect at a concentration of 10-6 mol/l ( 945.7+/-98.3 pg/ml compared with 180.9+/-31.2 pg/ml and 1720.4+/-690.1 pg/ml compared with 824.0+/-206.2 pg/ml, P < 0.001 respectively ) ... CRP and LPS could induce IL-6 release in human monocytes and simvastatin could inhibit this response in a dose dependent manner, which may provide an insight into the mechanisms of anti-inflammatory or anti-atherosclerotic actions of simvastatin
Ganapathi et al., Biochem J 1992 (Carcinoma, Hepatocellular...) : Okadaic acid ( OA ), a specific inhibitor of protein phosphatases 1 and 2A, inhibited in a dose dependent manner ( 5-20 nM ) the induction of C-reactive protein (CRP) , serum amyloid A (SAA) and fibrinogen by interleukin-6 (IL-6) plus interleukin-1 (IL-1), and of fibrinogen by IL-6 alone, in Hep 3B cells ... OA also inhibited the induction of CRP , fibrinogen and alpha 1-PI by IL-6 in the NPLC/PRF/5 cell line, albeit at a higher concentration ( 80 nM )
Ballou et al., Cytokine 1992 : CRP induced the rapid release of each cytokine, with significantly elevated levels in culture supernatants at 4 hours and maximal levels of TNF-alpha at 8 hours, and of IL-1 beta and IL-6 at 16 hours of culture
Li et al., Med Hypotheses 2004 (Acute-Phase Reaction...) : In our recent study, the results demonstrate that monocytes exhibit an enhanced production of interleukin-6 (IL-6) in response to CRP , and this response is significantly inhibited by simvastatin in a dose dependent manner
McCarty et al., Med Hypotheses 2004 : A recent study shows that nitric oxide suppresses the activation of Stat3 by interleukin-6 in hepatocytes ; Stat3 is crucial for the IL-6 mediated induction of CRP and various other acute phase reactants
Ogiwara et al., Rinsho Byori 2004 (Arteriosclerosis...) : CRP is produced in the liver in response to interleukin-6 (IL-6) , it is an acute phase reactant and used as a general inflammatory marker
Ivashchenko et al., Arterioscler Thromb Vasc Biol 2005 (Carcinoma, Hepatocellular...) : Interleukin-1beta (IL-1beta) and IL-6 stimulate CRP synthesis in hepatocytes
Li et al., Clin Chim Acta 2005 (Angina, Unstable) : CRP induced the enhanced release of IL-6 and tnf-alpha by 17-fold and 23-fold increase, respectively, in patients with unstable angina, while it did about 11-fold and 19-fold increase in patients with stable angina and normal group ( IL-6 : 3129+/-333 vs. 991+/-134 and 987+/-102 pg/ml, p < 0.01, respectively ; tnf-alpha : 1554+/-784 vs. 560+/-135 and 558+/-152 pg/ml, p < 0.01, respectively )
Yamaguchi et al., J Dent Res 2005 (Insulin Resistance) : CRP is produced by hepatocytes in response to interleukin-6 (IL-6)
Czarkowska-Paczek et al., Immunol Lett 2005 : We conclude that under certain circumstances, acute, pulsatile release of IL-6 does not stimulate synthesis of CRP
Blay et al., Cancer Res 1992 (Carcinoma, Renal Cell...) : Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 is involved in CRP increase in these patients
Rossi et al., Bone Marrow Transplant 2005 (Mucositis...) : Our results show ( 1 ) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production ; ( 2 ) no haematological toxicity ; ( 3 ) a significant reduction of mucositis and fever ; ( 4 ) a median event-free survival of 35 months and an overall survival of 68.2 % at 5 years with a median follow-up of 72 months ; and ( 5 ) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels
Voleti et al., J Immunol 2005 : In hepatoma Hep3B cells, IL-6 induces CRP expression by activating transcription factors STAT3 and C/EBPbeta
Sawczenko et al., Proc Natl Acad Sci U S A 2005 (Colitis...) : Also, the patients with the IL-6 GG genotype had higher circulating levels of C-reactive protein , an IL-6 induced product ( 36 vs. 18 mg/dl, P = 0.028 )
Anty et al., Am J Gastroenterol 2006 (Diabetes Mellitus, Type 2...) : The role of interleukin-6 (IL6) and lipopolysaccharide in CRP expression was also evaluated in subcutaneous adipose tissue obtained during cosmetic abdominoplasty ... In human adipose tissue, CRP mRNA levels were positively correlated with those of IL-6 and the CRP expression was enhanced in vitro by IL-6 and lipopolysaccharide
Yoshida et al., Life Sci 2006 : In this study, we examined whether pigment epithelium derived factor (PEDF) could block the interleukin-6 induced CRP expression in cultured human hepatoma cells and the way that it might achieve this effect ... PEDF inhibited the IL-6 induced CRP expression in Hep3B cells at both mRNA and proteins levels
Rachoń et al., Menopause 2006 : They also support the hypothesis that CRP increase during oral estrogen treatment is not mediated by the enhancement of interleukin-6 production by the immune cells but is rather caused by the hepatic first-pass metabolism effect
Fischer et al., Scand J Med Sci Sports 2007 (Obesity) : As C-reactive protein (CRP) is induced by IL-6 , we hypothesized that basal levels of IL-6 and CRP reflect the degree of regular physical activity when compared with other markers of inflammation associated with lifestyle related morbidity
Haider et al., Clin Exp Immunol 2006 (Endotoxemia) : LPS, interleukin (IL)-1 , IL-6 and tumour necrosis factor (TNF)-alpha increased and IL-10 reduced CRP expression in PBMC
Taylor et al., Inflammation 1991 (Carcinoma, Hepatocellular...) : Alpha-2-macroglobulin (alpha 2-M), a serum protease inhibitor that also binds cytokines, neutralized the inhibitory effect exerted by transforming growth factor-beta ( TGF-beta ) on IL-6 induced C-reactive protein (CRP) production by the human hepatoma cell line PLC/PRF/5 ... alpha 2-M was found to bind noncovalently with TGF-beta to form a complex that, upon acidification, released TGF-beta inhibitory activity as detected by IL-6 induced CRP production
Chang et al., J Cardiovasc Pharmacol 2007 : Experimental results showed that the effect of CRP on VCAM-1 expression and supernatant levels of MCP-1 and IL-6 increases stepwise as CRP concentrations increase from 25 to 50 to 75 to 100 microg/mL ( all P < 0.001 ) ... The effect of CRP on VCAM-1 expression in HUVECs and supernatant levels of MCP-1 and IL-6 were significantly suppressed by 25 micromol/L simvastatin with stepwise increased suppression as simvastatin dose increased to 50, 75, and 100 micromol/L ( all P < 0.0001 ). However, losartan did not significantly suppress CRP 's effect on VCAM-1 expression in HUVECs ( P > 0.5 )
Kino et al., J Allergy Clin Immunol 2007 : TB-2-081 suppressed IL-6 induced mRNA expression of alpha1-acid glycoprotein, alpha2-macroglobulin, and beta-fibrinogen in and secretion of the C-reactive protein by rat primary hepatocytes
Kino et al., Eur J Clin Invest 2007 (Acute-Phase Reaction...) : The compound also suppressed interleukin-6 induced mRNA expression of alpha2-acid glycoprotein, beta-fibrinogen and alpha2-macroglobulin in and the secretion of C-reactive protein by rat primary hepatocytes
Abe et al., Rinsho Ketsueki 1991 (Multiple Myeloma) : It was of interest that C-reactive protein , induced by IL-6 , was a good marker reflecting disease activity
Mayer et al., Int J Clin Pharmacol Ther 2007 : Rosuvastatin reduces interleukin-6 induced expression of C-reactive protein in human hepatocytes in a STAT3- and C/EBP dependent fashion ... IL-6 increased CRP secretion by up to 5-fold in Hep3B and 6.6-fold in PHH ... Our results show a direct inhibitory effect of rosuvastatin on IL-6 induced expression of CRP in liver cells
Yang et al., Cancer Cell 2007 (Multiple Myeloma) : CRP also enhanced myeloma cell secretion of IL-6 and synergized with IL-6 to protect myeloma cells from chemotherapy drug induced apoptosis
Nishikawa et al., J Immunol 2008 : In the early induction phase, IL-1 inhibited IL-6 mediated CRP gene expression, and NF-kappaB p65 inhibited the luciferase activity of pGL3-CRP by IL-1 plus IL-6 even in the presence of overexpressed STAT3
Peroś-Golubicić et al., Acta Med Iugosl 1991 (Lung Diseases...) : It is well known that interleukin-1 , among other functions, stimulates the hepatic production of C-reactive protein
Zhang et al., Biochem Biophys Res Commun 2009 (Acute-Phase Reaction) : Suppression of interleukin-6 induced C-reactive protein expression by FXR agonists ... In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6 induced CRP expression in human Hep3B hepatoma cells ... Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production
Elovainio et al., Occup Environ Med 2010 (Inflammation...) : In men, low organisational justice was associated with increased CRP levels at both follow-ups ( phase 3 and 7 ) and increased IL-6 at the second follow-up ( phase 7 )
de Vries et al., Cancer Res 1991 (Carcinoma...) : Tumor necrosis factor alpha and C-reactive protein serum levels increased during GM-CSF administration at the 6-micrograms dose level, but interleukin 6 serum levels were not affected
Oguz et al., Mycoses 2011 (Bacteremia...) : C-reactive protein and interleukin-6 responses for differentiating fungal and bacterial aetiology in late-onset neonatal sepsis
Kruger et al., Nutrition 2010 (Growth Disorders...) : Regression analyses showed that insulin resistance, diastolic blood pressure, and C-reactive protein contributed significantly to interleukin-6 in boys
Yap et al., Biochim Biophys Acta 1991 : ( 3 ) Since anti-TNF enhances the stimulatory effect of IL-6 on the synthesis of CRP and SAA, it seems likely that TNF is also produced by the human hepatocytes
Peng et al., Life Sci 2010 : The results showed that both IL-6 and Ang II increased CRP levels in the supernatant of VSMCs and induced mRNA and protein expression of CRP in VSMCs, whereas pretreatment of the cells with EGCG ( 1 x 10 ( -6 ) M, 3 x 10 ( -6 ) M, 10 x 10 ( -6 ) M ) significantly inhibited IL-6- and Ang II-induced production and expression of CRP in VSMCs in a concentration dependent manner
Lands et al., J Med Food 2010 (Cystic Fibrosis...) : Anthropometric measures, pulmonary function, serum C-reactive protein (CRP) , whole blood glutathione, and whole blood IL-8 and IL-6 responses to phytohemagglutinin ( PHA ) stimulation were measured at baseline and at 1 month
Kita et al., Hypertens Res 2010 (Hyperaldosteronism) : In addition, a mild but significant increase in C-reactive protein (CRP) mediated by interleukin-6 was observed during AM infusion in every participant, without exception
McNair et al., Mol Cell Biochem 2010 (Myocardial Infarction) : High sensitivity C-reactive protein ( hs-CRP ) is synthesized mainly by hepatocytes in response to tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interleukin-6 (IL-6)
Liou et al., J Microbiol Immunol Infect 2010 (Lupus Erythematosus, Systemic) : We have previously reported that lupus monocytes display distinctively differing patterns of C-reactive protein (CRP) inducing cytokine interleukin (IL)-6 , IL-1beta, and tumor necrosis factor (TNF)-alpha secretion when stimulated with either immune complexes ( ICs ) or lipopolysaccharide (LPS)
Liang et al., Eur J Pharmacol 2010 (Cardiomyopathies) : CRP increased PPARdelta and interleukin-6 expression in cardiomyocytes and H9c2 cardiomyoblasts
Majello et al., EMBO J 1990 (Carcinoma, Hepatocellular...) : Transcription of the human C-reactive protein (CRP) gene is induced by interleukin-6 (IL-6) during acute inflammation
Cruickshank et al., Clin Sci (Lond) 1990 : Our results are consistent with a role for interleukin-6 in the induction of C-reactive protein synthesis
Peyrin-Biroulet et al., Gut 2012 (Colitis, Ulcerative...) : Escherichia coli ( 1230 ± 175-fold, p < 0.01 ), lipopolysaccharide ( 26 ± 0.5-fold, p < 0.01 ), tumour necrosis factor a ( 15 ± 0.3-fold, p < 0.01 ) and interleukin-6 ( 10 ± 0.7-fold, p < 0.05 ) increased CRP mRNA levels in adipocyte 3T3-L1 cells
Lv et al., Eur J Pharm Sci 2012 (Atherosclerosis) : Ursolic acid suppresses IL-6 induced C-reactive protein expression in HepG2 and protects HUVECs from injury induced by CRP ... To investigate the inhibitory effects of ursolic acid ( UA ) on the expression of C-reactive protein (CRP) induced by IL-6 in HepG2 cells and the protective effects on the CRP induced injury to human umbilical vein endothelial cells ( HUVECs ) ... IL-6 can significantly increase CRP protein and mRNA expression in HepG2 cells, and this effect of IL-6 can be decreased by UA ( 6.25, 12.5, 25 µmol/L ) markedly in a dose dependent manner
Yang et al., Curr Drug Metab 2012 : SOCS-3, CRP , and LBP were extensively induced by IL-6 , with maximal induction observed at 2 ( SOCS-3 ) and 12 hrs ( CRP ; LBP ), demonstrating that the cultured human hepatocytes responded to IL-6 treatment
Busch et al., Mol Immunol 2013 : IL-6 or C3a impaired the CRP gene expression
Li et al., Pharmacol Rep 2012 (Cardiovascular Diseases...) : Epigallocatechin-3-gallate inhibits angiotensin II and interleukin-6 induced C-reactive protein production in macrophages ... Therefore, the effect of EGCG on angiotensin II (Ang II)- and interleukin-6 (IL-6) induced CRP production in U937 macrophages and the possible mechanisms were observed
Zhou et al., Heart 2013 (Ion Channel Gating...) : Interleukin (IL)-6 treatment did not induce CRP expression in vessel rings of white rabbits in the absence of mechanical strain ... These results indicate that the inflammatory cytokine IL-6 alone does not induce CRP synthesis in vessels in the absence of mechanical strain ; however, IL-6 augments mechanical strain induced CRP synthesis in vessels via the stretch activated channel-NF-?B pathway
Wang et al., Mol Cell Biochem 2013 : C-reactive protein (CRP) , an acute phase protein in humans, is predominantly produced by hepatocytes in response to interleukin-6 (IL-6) ... The aims of this study were to examine the effect of the n-3 PUFAs, docosahexaenoic acid ( DHA ), and eicosapentaenoic acid ( EPA ), on the modulation of IL-6 induced CRP expression and to explore its possible mechanisms ... Knockdown of Signal Transducer and Activator of Transcription 3 ( STAT3 ) and CCAAT box/Enhancer Binding Protein ß ( C/EBPß ) by small interfering RNAs ( siRNAs ) significantly decreased IL-6 induced CRP promoter activity ... Taken together, our results demonstrate that DHA and EPA are able to reduce IL-6 induced CRP expression in HepG2 cells via an inhibition of STAT3 activation
Bizheh et al., Iranian journal of basic medical sciences 2011 : Moreover, muscle derived interleukin-6 ( a stimulator of glycogenolysis in the liver ) induces hepatic production of CRP
Mackiewicz et al., Biochem J 1988 : While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis
Swaak et al., Rheumatol Int 1989 (Acute-Phase Reaction...) : Our results are in agreement with the findings that IL-6 might be responsible for the CRP response
Moshage et al., Biochem Biophys Res Commun 1988 : These findings suggest that IL-6 plays a key role in the stimulation of synthesis of serum amyloid A and C-reactive protein by the human liver cells
Zhang et al., Biochem J 1995 : The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is exerted at the transcriptional level
Ku et al., Cytokine 1993 (Carcinoma, Hepatocellular...) : The mouse C-reactive protein (CRP) gene is expressed in response to IL-1 but not IL-6
Buck et al., Pediatrics 1994 (Bacterial Infections) : As interleukin-6 (Il-6) plays a critical role in the induction of C-reactive protein (CRP) synthesis in the liver, it was hypothesized that this cytokine could be detected earlier in blood than the CRP during the course of bacterial infection
Li et al., Biochemistry 1996 (Carcinoma, Hepatocellular) : To study the mechanism of interleukin-6 (IL-6) induction of human C-reactive protein (CRP) gene expression, we have utilized a human hepatoma ( PLC/PRF/5 ) cell culture system to analyze the trans acting factors which bind to the 300 bp 5'-flanking region of human CRP gene
Wigmore et al., Ann Surg 1997 : Eicosapentaenoic and gammalinolenic significantly increased interleukin-6 stimulated production of C-reactive protein and alpha 1-antichymotrypsin but reversed the stimulatory effect of interleukin-6 on haptoglobin production
Weinhold et al., Biochem J 1997 (Wounds and Injuries) : Interleukin-6 dependent and -independent regulation of the human C-reactive protein gene
Gabay et al., Blood 1999 (Liver Neoplasms) : In contrast to IL-1Ra, production of C-reactive protein by human primary hepatocytes was stimulated by IL-6 and decreased by the addition of IL-4