NF-κB/PPARγ and/or AP-1/PPARγ ‘on/off’ switches and induction of CBP in colon adenocarcinomas: correlation with COX-2 expression

Konstantinopoulos, Panagiotis A.; Vandoros, Gerasimos P.; Sotiropoulou-Bonikou, Georgia; Kominea, Athina; Papavassiliou, Athanasios G.

doi:10.1007/s00384-006-0112-y

Cited by 54 publications

(36 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, the activation of CB2 and/or PPAR␥ significantly reduces CXCL1/KC and MIP-2 tissue levels 71,72 and inhibits NF B, IKK␣/␤, and CREB activation. 45,[73][74][75] As we have noted, all of these effects were observed in the colons from mice treated with BCP. Collectively, therefore, these data reinforce the important role of CB2 and PPAR␥ activation in BCP antiinflammatory activity.…”

Section: Discussionmentioning

confidence: 98%

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

Bento

Marcon

Dutra

et al. 2011

The American Journal of Pathology

212

145

View full text Add to dashboard Cite

Cannabinoid receptor 2 (CB2) activation is suggested to trigger the peroxisome proliferator-activated receptor-␥ (PPAR␥) pathway, and agonists of both receptors improve colitis. Recently, the plant metabolite (E)-␤-caryophyllene (BCP) was shown to bind to and activate CB2. In this study, we examined the antiinflammatory effect of BCP in dextran sulfate sodium (DSS)-induced colitis and analyzed whether this effect was mediated by CB2 and PPAR␥. Oral treatment with BCP reduced disease activity, colonic macro-and microscopic damage, myeloperoxidase and N-acetylglucosaminidase activities, and levels and mRNA expression of colonic tumor necrosis factor-␣, IL-1␤, interferon-␥, and keratinocyte-derived chemokine. Inflammatory bowel diseases (IBDs) are a group of chronic diseases that affect the gastrointestinal tract and have been mainly subdivided as ulcerative colitis and Crohn's disease. 1 The IBDs are characterized by a strong leukocyte activation and infiltration into the intestinal tissues, the release of proinflammatory cytokines 2 and enzymes, and the formation of reactive oxygen species. All of these events can induce an extensive and unbalanced activation of the mucosal immune system, driven by the commensal flora. 3 Recent evidence suggests a role for the cannabinoid system in IBD regulation. Cannabinoid receptors 1 and 2 (CB1 and CB2) are expressed in normal human colon 4,5 and are up-regulated in IBD colonic tissue. In addition, an enhanced level of endocannabinoids was found in biopsy specimens from patients with ulcerative colitis. 5 It is thought that CB1 activation results in a decrease of intestinal hypermotility and hypersecretion, whereas the activation of CB2 results in the inhibition of proinflammatory mediators. In addition, both CB2 and CB1 knockout mice are more susceptible to the development of experimental colitis, and the activation of these receptors is extremely important for the abrogation of intestinal inflammation. 6 The role of CB2, however, is directly involved with innate immune system, because CB2 is primarily expressed in immune cells, such as macrophages, CD4 ϩ and CD8 ϩ T cells, monocytes, and polymorphonuclear neutro-

show abstract

Section: Discussionmentioning

confidence: 98%

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

Bento

Marcon

Dutra

et al. 2011

The American Journal of Pathology

212

145

View full text Add to dashboard Cite

show abstract

“…Our results suggest that IFNγ downregulates CD36 primarily by preventing PPARγ activation as opposed to reducing PPARγ expression. It is possible that IFNγ signaling through STAT1 causes a sequestering of the coactivator proteins CREB binding protein (CBP) and p300 which are in limiting amounts in the cell [47][48][49][50]. Since PPARγ and STAT1 are in competition for cellular CBP and p300, this would prevent PPARγ activation by rosiglitazone.…”

Section: Discussionmentioning

confidence: 99%

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

Chu¹,

Tai²,

Beer³

et al. 2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumour necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ did prevent the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression.

show abstract

“…These genes included Timp3 , Ptpn11 , antagonists of reactive oxygen species ( Cat , Gss , Sod1 ) and nuclear receptors. Nuclear receptors such as Lxra , Pparg and Rora have been shown to interfere with NFκB and AP-1 activation [39-41], and to have anti-inflammatory and arthritis-suppressive properties [42-45]. Rxrg was another nuclear receptor expressed in significantly increased levels in DA.F344(Cia5a) congenics.…”

Section: Discussionmentioning

confidence: 99%

The arthritis severity locus Cia5a regulates the expression of inflammatory mediators including Syk pathway genes and proteases in pristane-induced arthritis

Gulko

2012

BMC Genomics

View full text Add to dashboard Cite

BackgroundCia5a is a locus on rat chromosome 10 that regulates disease severity and joint damage in two models of rheumatoid arthritis, collagen- and pristane-induced arthritis (PIA). In this study, we aimed to identify cellular and molecular processes regulated by Cia5a using microarray-based gene expression analysis of synovial tissues from MHC identical DA (severe erosive disease) and DA.F344(Cia5a) congenics (mild non-erosive disease) rats.ResultsSynovial tissues from six DA and eight DA.F344(Cia5a) rats were analyzed 21 days after the induction of PIA using the Illumina RatRef-12 BeadChip (21,922 genes) and selected data confirmed with qPCR. There was a significantly increased expression of pro-inflammatory mediators such as Il1b (5-fold), Il18 (3.9-fold), Cxcl1 (10-fold), Cxcl13 (7.5-fold) and Ccl7 (7.9-fold), and proteases like Mmp3 (23-fold), Mmp9 (32-fold), Mmp14 (4.4-fold) and cathepsins in synovial tissues from DA, with reciprocally reduced levels in congenics. mRNA levels of 47 members of the Spleen Tyrosine Kinase (Syk) pathway were significantly increased in DA synovial tissues compared with DA.F344(Cia5a), and included Syk (5.4-fold), Syk-activating receptors and interacting proteins, and genes regulated by Syk such as NFkB, and NAPDH oxidase complex genes. Nuclear receptors (NR) such as Rxrg, Pparg and Rev-erba were increased in the protected congenics, and so was the anti-inflammatory NR-target gene Scd1 (54-fold increase). Tnn (72-fold decrease) was the gene most significantly increased in DA.ConclusionsAnalyses of gene expression in synovial tissues revealed that the arthritis severity locus Cia5a regulates the expression of key mediators of inflammation and joint damage, as well as the expression of members of the Syk pathway. This expression pattern correlates with disease severity and joint damage and along with the gene accounting for Cia5a could become a useful biomarker to identify patients at increased risk for severe and erosive disease. The identification of the gene accounting for Cia5a has the potential to generate a new and important target for therapy and prognosis.

show abstract

NF-κB/PPARγ and/or AP-1/PPARγ ‘on/off’ switches and induction of CBP in colon adenocarcinomas: correlation with COX-2 expression

Cited by 54 publications

References 40 publications

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

β-Caryophyllene Inhibits Dextran Sulfate Sodium-Induced Colitis in Mice through CB2 Receptor Activation and PPARγ Pathway

Macrophage heterogeneity and cholesterol homeostasis: Classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL

The arthritis severity locus Cia5a regulates the expression of inflammatory mediators including Syk pathway genes and proteases in pristane-induced arthritis

Contact Info

Product

Resources

About