Protein Information

Name IL 6
Synonyms 26 kd protein; B cell differentiation factor; B cell stimulatory factor 2; BSF 2; BSF2; CDF; CTL differentiation factor; HGF…

Compound Information

Name cycloheximide
CAS

Reference List

PubMed Abstract RScore(About this table)
16883635 Lee KH, Choi EM: Rubus coreanus Miq. extract promotes osteoblast differentiation and inhibits bone-resorbing mediators in MC3T3-E1 cells. Am J Chin Med. 2006;34(4):643-54.

The effect of RCE (50 microg/ml) in increasing cell viability, ALP activity, and collagen content was prevented by the presence of 10 (-6) M cycloheximide and 10 (-6) M tamoxifen, suggesting that RCE's effect results from a newly synthesized protein component and might be partly involved in estrogen action.
Treatment with RCE (10approximately50 microg/ml) decreased the 0.2 mM H (2) O (2)-induced apoptosis and production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and nitric oxide (NO) in osteoblasts.
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19395591 Kumagai K, Ito K, Ando Y, Hakamata S, Teranishi M, Nakayama H, Manabe S: Neutralization of IL-10 exacerbates cycloheximide-induced hepatocellular apoptosis and necrosis. Toxicol Pathol. 2009;37(4):536-46. Epub 2009 Apr 24.

Blocking IL-10 in the IL-10Ab/CHX group led to greater increases in hepatic mRNA and serum levels of proinflammatory cytokines, such as TNF-alpha and IL-6.
1(0,0,0,1) Details
19248116 Yammani RR, Long D, Loeser RF: Interleukin-7 stimulates secretion of S100A4 by activating the JAK/STAT signaling pathway in human articular chondrocytes. Arthritis Rheum. 2009 Mar;60(3):792-800.

METHODS: Human articular chondrocytes isolated from ankle cartilage were stimulated with 10 ng/ml of interleukin-1beta (IL-1beta), IL-6, IL-7, or IL-8.
Cells were pretreated with either a JAK-3 inhibitor, brefeldin A, or cycloheximide.
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17286758 Endoh I, Di Girolamo N, Hampartzoumian T, Cameron B, Geczy CL, Tedla N: Ultraviolet B irradiation selectively increases the production of interleukin-8 in human cord blood-derived mast cells. Clin Exp Immunol. 2007 Apr;148(1):161-7.

UVB exposure significantly increased the release of interleukin (IL)-8 and modestly increased IL-1alpha production, but cytokines such as IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma were unaffected.
Cycloheximide reduced the UVB-mediated induction of IL-8 by 30-40%, suggesting that new protein synthesis contributed to IL-8 production.
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15722640 Park CS, Choi EN, Kim JS, Choi YS, Rhim TY, Chang HS, Chung IY: Interferon-gamma inhibits in vitro mobilization of eosinophils by interleukin-5. Int Arch Allergy Immunol. 2005 Mar;136(3):295-302. Epub 2005 Feb 16.

RESULTS: Interleukin (IL)-5, IL-6, and tumor necrosis factor (TNF) induced an eosinophil shape change, whereas interferon (IFN)-gamma significantly inhibited the shape change.
We further analyzed the IFN-gamma effect, showing that pretreatment with IFN-gamma strongly suppressed IL-5-induced eosinophil shape change, and cycloheximide (CHX) abrogated the suppression by IFN-gamma, suggesting that new protein synthesis is required for the inhibitory effect by this cytokine.
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15879116 Xing L, Remick DG: Mechanisms of dimethyl sulfoxide augmentation of IL-1 beta production. . J Immunol. 2005 May 15;174(10):6195-202.

This study demonstrated that 1% DMSO increased LPS-stimulated (50 ng/ml) IL-1beta secretion in a dose- and time-dependent manner without altering TNF or IL-6.
Cycloheximide studies demonstrated that the DMSO augmentation of IL-1beta mRNA did not require de novo protein synthesis, and studies with actinomycin D showed that DMSO did not alter the half-life of IL-1beta mRNA, suggesting that DMSO did not change the stability of IL-1beta mRNA.
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17671691 Kamohara H, Takahashi M, Ishiko T, Ogawa M, Baba H: Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: Impact of CXCL-8 as an autocrine growth factor. Int J Oncol. 2007 Sep;31(3):627-32.


Actinomycin D suppressed and cycloheximide augmented CXCL-8 mRNA which was induced by TNF-alpha or not.
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16204952 Lee KH, Choi EM: Biochanin A stimulates osteoblastic differentiation and inhibits hydrogen peroxide-induced production of inflammatory mediators in MC3T3-E1 cells. Biol Pharm Bull. 2005 Oct;28(10):1948-53.


The effect of biochanin A (10 microM) in increasing ALP activity and collagen content was completely prevented by the presence of 10 (-6) M cycloheximide and 10 (-6) M tamoxifen, suggesting that biochanin A's effect results from a newly synthesized protein component and might be partly involved in estrogen action.
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16237104 Mandal P, Novotny M, Hamilton TA: Lipopolysaccharide induces formyl peptide receptor 1 gene expression in macrophages and neutrophils via transcriptional and posttranscriptional mechanisms. J Immunol. 2005 Nov 1;175(9):6085-91.


First, the response to LPS is partially blocked by the translational inhibitor cycloheximide.
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18005266 Ratthe C, Girard D: Investigation of the interleukin (IL)-4/IL-4 receptor system in promyelocytic leukaemia PLB-985 cells during differentiation toward neutrophil-like phenotype: mechanism involved in IL-4-induced SOCS3 protein expression. Br J Haematol. 2008 Jan;140(1):59-70. Epub 2007 Nov 12.


Utilization of catalase, cycloheximide and genistein inhibitors showed that IL-4 induced SOCS3 by a mechanism dependent on a complete NADPH oxidase complex, protein synthesis and tyrosine phosphorylation, but independent of production of reactive oxygen species.
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17529908 Xing L, Remick DG: Mechanisms of oxidant regulation of monocyte chemotactic protein 1 production in human whole blood and isolated mononuclear cells. Shock. 2007 Aug;28(2):178-85.


Cycloheximide treatment did not abolish the DMSO inhibition of MCP-1 mRNA, demonstrating that de novo protein synthesis is not required.
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19006119 Suh HN, Lee YJ, Han HJ: Interleukin-6 promotes 2-deoxyglucose uptake through p44/42 MAPKs activation via Ca2+/PKC and EGF receptor in primary cultured chicken hepatocytes. J Cell Physiol. 2009 Mar;218(3):643-52.

Indeed, IL-6 increased GLUT-2 mRNA and protein expression as well as 2-DG uptake, which were blocked by actinomycin D (AD, transcription inhibitor) and cycloheximide (CHX, translation inhibitor).
41(0,1,1,11) Details
17101148 Reil JC, Gilles S, Zahler S, Brandl A, Drexler H, Hultner L, Matrisian LM, Welsch U, Becker BF: Insights from knock-out models concerning postischemic release of TNFalpha from isolated mouse hearts. J Mol Cell Cardiol. 2007 Jan;42(1):133-41. Epub 2006 Nov 13.

We employed hearts of various mice knock-out strains (interleukin-6 (-/-), matrix metalloprotease-7 (-/-), mast-cell deficient WBB6F1-Kit (W)/Kit (W-v), TNF-R1 (-/-)) and wildtype mice, the latter perfused without and with infusion of cycloheximide or TNFalpha-cleaving-enzyme inhibitor (TAPI-2).
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17197193 Fritzenwanger M, Meusel K, Foerster M, Kuethe F, Krack A, Figulla HR: Cardiotrophin-1 induces interleukin-6 synthesis in human umbilical vein endothelial cells. Cytokine. 2006 Nov;36(3-4):101-6. Epub 2007 Jan 2.

For the pathway determination following inhibitors were used: piceatannol (signal transducer and activation of transcription (STAT) 3 phosphorylation), wortmannin (phosphatiylinositol 3-kinase (PI3K)), SB203580 (p38 mitogen-activated protein kinase (MAPK)), AG490 (Janus kinase (JAK) 2), PD98059 (mitogen-activated protein kinase kinase (MEK) 1/2), parthenolide (nuclear factor kappaB) and cycloheximide (protein biosynthesis).
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19578789 Kamimoto M, Mizuno S, Nakamura T: Reciprocal regulation of IL-6 and IL-10 balance by HGF via recruitment of heme oxygenase-1 in macrophages for attenuation of liver injury in a mouse model of endotoxemia. Int J Mol Med. 2009 Aug;24(2):161-70.

In the culture of macrophages (Raw264.7), HGF enhanced the LPS-mediated HO-1 induction, and this effect was abolished by cycloheximide, but not by actinomycin-D, thus suggesting that a post-transcriptional pathway is involved in HGF-mediated up-regulation of HO-1.
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19071214 Lee BS, Park M, Cha HY, Lee JH: Hepatocyte growth factor induces delayed STAT3 phosphorylation through interleukin-6 expression. Cell Signal. 2009 Mar;21(3):419-27. Epub 2008 Nov 30.

Blocking of the phosphorylation by cycloheximide or actinomycin D and the rapid STAT3 phosphorylation with the conditioned medium from HGF/SF-treated NIH3T3 cells suggested that a newly synthesized secretory protein was responsible for the delayed STAT3 phosphorylation.
4(0,0,0,4) Details
19664126 Misiak-Tloczek A, Brzezinska-Blaszczyk E: IL-6, but not IL-4, stimulates chemokinesis and TNF stimulates chemotaxis of tissue mast cells: involvement of both mitogen-activated protein kinases and phosphatidylinositol 3-kinase signalling pathways. APMIS. 2009 Aug;117(8):558-67.


Considering that interleukin (IL)-6 and IL-4, as well as tumour necrosis factor (TNF), influence mast cell activity in various ways, the purpose of the current study was to examine whether these cytokines function as rat peritoneal mast cell chemoattractants.
7(0,0,0,7) Details
17064399 Kubota K, Sakaki H, Imaizumi T, Nakagawa H, Kusumi A, Kobayashi W, Satoh K, Kimura H: Retinoic acid-inducible gene-I is induced in gingival fibroblasts by lipopolysaccharide or poly IC: possible roles in interleukin-1beta, -6 and -8 expression. Oral Microbiol Immunol. 2006 Dec;21(6):399-406.

We also addressed the role of RIG-I in the expression of IL-1beta, IL-6 and IL-8 in gingival fibroblasts stimulated with LPS or dsRNA.
The effect of cycloheximide, a protein synthesis inhibitor, on RIG-I induction by these stimuli was examined.
4(0,0,0,4) Details
16192422 Yung S, Tsang RC, Sun Y, Leung JK, Chan TM: Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis. J Am Soc Nephrol. 2005 Nov;16(11):3281-94. Epub 2005 Sep 28.


Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect.
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16000871 Kim HJ, Rho YH, Choi SJ, Lee YH, Cheon H, Um JW, Sohn J, Song GG, Ji JD: 15-Deoxy-delta12,14-PGJ2 inhibits IL-6-induced Stat3 phosphorylation in lymphocytes. Exp Mol Med. 2005 Jun 30;37(3):179-85.

Although cycloheximide reversed 15d-PGJ (2)-mediated inhibition of Stat3 activation, actinomycin D had no effect on 15d-PGJ (2)-mediated inhibition of IL-6 signaling, indicating that inhibition of IL-6 signaling occur independent of de novo gene expression.
3(0,0,0,3) Details
17368935 Choi EM: Modulatory effects of luteolin on osteoblastic function and inflammatory mediators in osteoblastic MC3T3-E1 cells. Cell Biol Int. 2007 Sep;31(9):870-7. Epub 2007 Feb 11.

The effect of luteolin in increasing collagen content and ALP activity was completely prevented by the presence of 10 (-6) M cycloheximide and 10 (-6) M tamoxifen, suggesting that luteolin's effect results from a newly synthesized protein component and might be partly involved in estrogen action.
We then examined the effect of luteolin on the 3-morpholinosydnonimine (SIN-1)-induced production of oxidative stress markers [nitric oxide (NO) and prostaglan E (2) (PGE (2))] and cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)] in osteoblasts.
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17416199 Choi EM: Apigenin increases osteoblastic differentiation and inhibits tumor necrosis factor-alpha-induced production of interleukin-6 and nitric oxide in osteoblastic MC3T3-E1 cells. Pharmazie. 2007 Mar;62(3):216-20.

The effect of apigenin in increasing ALP activity and collagen content was completely prevented by the presence of 10 (-6) M cycloheximide and 10-6 M tamoxifen, suggesting that apigenin's effect results from a newly synthesized protein component and might be partly involved in estrogen action.
2(0,0,0,2) Details
19799897 Fritz DK, Kerr C, Botelho F, Stampfli M, Richards CD: Oncostatin M (OSM) primes IL-13- and IL-4-induced eotaxin responses in fibroblasts: regulation of the type-II IL-4 receptor chains IL-4Ralpha and IL-13Ralpha1. Exp Cell Res. 2009 Dec 10;315(20):3486-99. Epub 2009 Sep 30.


Oncostatin M (OSM), a pleiotropic cytokine and a member of the gp130/IL-6 cytokine family, has been implicated in regulation of various chronic inflammatory processes.
2(0,0,0,2) Details
19439980 Triggiani M, Granata F, Petraroli A, Loffredo S, Frattini A, Staiano RI, Monaco G, Marone G: Inhibition of secretory phospholipase A2-induced cytokine production in human lung macrophages by budesonide. Int Arch Allergy Immunol. 2009;150(2):144-55. Epub 2009 May 11.


At the end of incubation the release of TNF-alpha, IL-6 and IL-8 was assessed by ELISA.
2(0,0,0,2) Details
16157236 Su SJ, Huang LW, Pai LS, Liu HW, Chang KL: Homocysteine at pathophysiologic concentrations activates human monocyte and induces cytokine expression and inhibits macrophage migration inhibitory factor expression. Nutrition. 2005 Oct;21(10):994-1002.


METHODS: Human monocytes were treated in vitro with a variety of DL-homocysteine concentrations that ranged from physiologic concentration to higher than pathophysiologic concentration, and we analyzed their expressions of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8, interleukin-12, and migration inhibitory factor.
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18854426 Gu JQ, Ikuyama S, Wei P, Fan B, Oyama J, Inoguchi T, Nishimura J: Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages. Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1390-400. Epub 2008 Oct 14.

Actinomycin D almost completely abolished the LPS effect, whereas cycloheximide decreased the expression at 12 h, indicating that the LPS-induced ADRP expression was stimulated at the transcriptional level and was also mediated by new protein synthesis.
In addition, preceding the increase of the ADRP mRNA, LPS induced the expression of interleukin (IL)-6, IL-1alpha, and interferon-beta mRNAs, all of which stimulated the ADRP expression.
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16123165 Ishikawa T, Hwang K, Lazzarino D, Morris PL: Sertoli cell expression of steroidogenic acute regulatory protein-related lipid transfer 1 and 5 domain-containing proteins and sterol regulatory element binding protein-1 are interleukin-1beta regulated by activation of c-Jun N-terminal kinase and cyclooxygenase-2 and cytokine induction. Endocrinology. 2005 Dec;146(12):5100-11. Epub 2005 Aug 25.

IL-1beta rapidly decreases levels of precursor and mature sterol regulatory element-binding protein-1, changes not altered by cycloheximide, suggesting coordinate regulation of StARD1 and -D5, but not StARD4, expression.
Concomitantly, increases in IL-1alpha, IL-6, and IL-1beta mRNAs (1-3 h) are observed.
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16684952 Cohen M, Marchand-Adam S, Lecon-Malas V, Marchal-Somme J, Boutten A, Durand G, Crestani B, Dehoux M: HGF synthesis in human lung fibroblasts is regulated by oncostatin M. . Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1097-103.

Oncostatin M (OSM) is a IL-6 family cytokine locally produced in acute lung injury.
HGF was released in its cleaved mature form, and its secretion was completely inhibited in the presence of cycloheximide, indicating a de novo protein synthesis.
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15641051 Franchimont N, Lambert C, Huynen P, Ribbens C, Relic B, Chariot A, Bours V, Piette J, Merville MP, Malaise M: Interleukin-6 receptor shedding is enhanced by interleukin-1beta and tumor necrosis factor alpha and is partially mediated by tumor necrosis factor alpha-converting enzyme in osteoblast-like cells. Arthritis Rheum. 2005 Jan;52(1):84-93.

OBJECTIVE: Interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) activation of gp130 represents an alternative pathway for osteoclast development in inflammatory conditions.
This effect was not influenced by cycloheximide or 5,6-dichlorobenzimidazole riboside but was markedly inhibited by the calcium chelator EGTA and by the TACE and matrix metalloproteinase inhibitor hydroxamate (Ru36156).
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19331698 Wegrzyn P, Yarwood SJ, Fiegler N, Bzowska M, Koj A, Mizgalska D, Malicki S, Pajak M, Kasza A, Kachamakova-Trojanowska N, Bereta J, Jura J, Jura J: Mimitin - a novel cytokine-regulated mitochondrial protein. BMC Cell Biol. 2009 Mar 31;10:23.

The expression of mimitin is stimulated more than 1.6-fold by IL-1 and by IL-6, with the maximum level of mimitin observed after 18-24 h exposure to these cytokines.
However, when apoptosis was induced by TNF and cycloheximide, and mimitin expression blocked, the activities of these caspases were significantly increased.
1(0,0,0,1) Details
18729741 Shizu M, Itoh Y, Sunahara R, Chujo S, Hayashi H, Ide Y, Takii T, Koshiko M, Chung SW, Hayakawa K, Miyazawa K, Hirose K, Onozaki K: Cigarette smoke condensate upregulates the gene and protein expression of proinflammatory cytokines in human fibroblast-like synoviocyte line. J Interferon Cytokine Res. 2008 Aug;28(8):509-21.

When human fibroblast-like synoviocytes line MH7A was treated with cigarette smoke condensate (CSC), either mainstream or sidestream, expression levels of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, and CYP1A1 mRNA were upregulated in both time- and dose-dependent manners.
Cycloheximide treatment indicated that the augmenting effect of CSC on IL-1alpha, IL-1beta and IL-8, but not IL-6 and CYP1A1, mRNA expression requires de novo protein synthesis.
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17501665 Lambert C, Oury C, Dejardin E, Chariot A, Piette J, Malaise M, Merville MP, Franchimont N: Further insights in the mechanisms of interleukin-1beta stimulation of osteoprotegerin in osteoblast-like cells. J Bone Miner Res. 2007 Sep;22(9):1350-61.

Post-transcriptional effects were examined by using cycloheximide and actinomycin D.
MATERIALS AND METHODS: OPG mRNA levels in MG-63 cells were quantified by real-time RT-PCR and protein levels of OPG and IL-6 by ELISA.
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16988256 Dennis VA, Jefferson A, Singh SR, Ganapamo F, Philipp MT: Interleukin-10 anti-inflammatory response to Borrelia burgdorferi, the agent of Lyme disease: a possible role for suppressors of cytokine signaling 1 and 3. Infect Immun. 2006 Oct;74(10):5780-9.

Neither endogenous IL-10 nor the translation inhibitor cycloheximide blocked SOCS1/SOCS3 induction by B. burgdorferi and its lipoproteins, indicating that the expression of other genes is not required.
This temporally correlated with the IL-10-mediated inhibition of the inflammatory cytokines IL-1beta, IL-6, IL-12p40, IL-18, and tumor necrosis factor alpha.
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19289468 Kurada BR, Li LC, Mulherkar N, Subramanian M, Prasad KV, Prabhakar BS: MADD, a splice variant of IG20, is indispensable for MAPK activation and protection against apoptosis upon tumor necrosis factor-alpha treatment. J Biol Chem. 2009 May 15;284(20):13533-41. Epub 2009 Mar 16.

Abrogation of MADD expression rendered cells highly susceptible to TNFalpha-induced apoptosis in the absence of cycloheximide.
This observation was substantiated by an accompanying loss in the activation of p90RSK, a key downstream target of MAPK, whereas the NF-kappaB-regulated interleukin 6 levels remained unaffected.
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