Fish Oil Decreases Macrophage Tumor Necrosis Factor Gene Transcription by Altering the NFκB Activity

Lo, Chang-fa; Chiu, Ken C.; Fu, Minjuan; Lo, Rosa; Helton, Scott

doi:10.1006/jsre.1998.5524

Cited by 211 publications

(145 citation statements)

References 37 publications

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“…These products are important regulators of cellular function and can cause proinflammatory, atherogenic, and prothrombotic effects (42). On the other hand, 3 fatty acids, such as docosahexaenoic acid (C22:6n3) and eicosapentaenoic acid (C20:5n3), which were decreased on HFD, can antagonize the pro-inflammatory effects of 6 fatty acids and down-regulate inflammatory gene expression (43)(44)(45)(46)(47). Furthermore, treatment of obese mice and rats with 3 FAs improves insulin resistance (48,49).…”

Section: Discussionmentioning

confidence: 99%

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Lü

Nguyen

et al. 2010

Journal of Biological Chemistry

211

178

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Obesity represents a state of chronic, low grade inflammation and is associated with infiltration of increased numbers of adipose tissue macrophages (ATMs). Diet-induced obesity leads to an increase in non-inflammatory M1-like ATMs displaying the CD11c surface marker. We assessed the function of CD11c-positive ATMs when insulin resistant high fat diet (HFD) mice become insulin-sensitive after switching from HFD to normal chow (NC). HFD mice rapidly become insulin-sensitive in all major insulin-target tissues, including muscle, liver, and adipose tissue, after the diet switch. In adipose tissue the CD11c-positive macrophages remain constant in number despite the presence of insulin sensitivity, but these macrophages now assume a new phenotype in which they no longer exhibit increased inflammatory pathway markers. Adipose tissue markers of apoptosis and necrosis were elevated on HFD and remain high after the HFD 3 NC diet switch. Furthermore, ATM accumulation preceded detectable adipocyte necrosis at the early phase of HFD. Together, these results indicate that 1) CD11c-positive M1-like ATMs can exhibit phenotypic plasticity and that the polarization of these cells between inflammatory and non-inflammatory states is well correlated to the presence of absence of insulin resistance, and 2) adipocyte necrosis and apoptosis can be dissociated from ATM accumulation.

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Section: Discussionmentioning

confidence: 99%

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Lü

Nguyen

et al. 2010

Journal of Biological Chemistry

211

178

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“…In this study, LPS challenge in chickens resulted in increased abundance of NFkB mRNA (Table 7). Lo et al (1998) reported that fish oil decreased macrophage TNFa gene transcription by altering the NFkB activity. It is believed that the NFkB plays an important role in the production of pro-inflammatory cytokines in chickens challenged with LPS.…”

Section: Discussionmentioning

confidence: 99%

Growth performance and immune responses in chickens after challenge with lipopolysaccharide and modulation by dietary different oils

Yang

Guo

et al. 2008

Animal

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The study was conducted to investigate the effects of different oils on growth performance and immune responses of chickens after challenge with lipopolysaccharide (LPS). A total of 288 chickens were assigned in a 2 3 2 factorial design. Factors were dietary fat type (4.5% maize oil or 4.5% fish oil) and immunological challenge (LPS or saline). At 20 days and 27 days of age, chickens were injected intraperitoneally with either 1 mg/kg body weight of LPS or sterile saline. LPS decreased feed intake from 21 days to 28 days of age and body-weight gain from 21 days to 42 days of age. Fish oil improved feed-conversion efficiency of chickens after LPS challenge for the first time. Fish oil supplementation decreased lymphocyte proliferation (21 days: P , 0.0001; 28 days: P , 0.0001) and the ratio of CD3 1 CD4 1 /CD3 1 CD8 1 (21 days: P 5 0.0479; 28 days: P 5 0.0009) after LPS challenge. LPS challenge increased the levels of interleukin-1 (IL-1) (21 days: P , 0.0001; 28 days: P 5 0.0030), IL-6 (21 days: P , 0.0001; 28 days: P 5 0.0001) and tumor necrosis factor-a (TNF-a) (21 days: P 5 0.0008; 28 days: P 5 0.0018). And fish oil alleviated the elevations in the production of IL-6 (21 days: P 5 0.0359; 28 days: P 5 0.0302) and TNF-a (21 days: P 5 0.0055; 28 days: P 5 0.0391) induced by the LPS challenge. Fish oil alleviated the mRNA abundance elevation of nuclear factor kappa B (NFkB) (21 days: P 5 0.0079; 28 days: P 5 0.0017) after LPS challenge. These results showed that fish oil acts as an anti-inflammatory agent, which may be associated with down-regulation of the activated immune system. The results of pro-inflammatory cytokines and mRNA abundance results suggested that fish oil might alleviate the elevation of IL-6 and TNF-a induced by LPS through down-regulating NFkB expression.

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“…In this regard, Liu et al, (2001) showed that in a mouse epidermal cell system, w3-PUFAs, but not the w6-arachidonic acid, effectively inhibited growth factor-triggered activator protein-1 transactivation. Moreover, w3-PUFAs down-regulated cytokine-triggered NF-kB activation and subsequent gene transcription in endothelial cells (McGuinness et al, 2008) as well as in macrophages (Lo et al, 1999). However, the direct PUFA target was not addressed in any of these studies.…”

Section: Figurementioning

confidence: 97%

The ω3‐polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A₂ and suppress PGE₂ formation in mesangial cells

Huwiler

Feuerherm

Sakem

et al. 2012

British J Pharmacology

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BACKGROUND AND PURPOSEw3-polyunsaturated fatty acids (w3-PUFAs) are known to exert anti-inflammatory effects in various disease models although their direct targets are only poorly characterized. EXPERIMENTAL APPROACHHere we report on two new cPLA2 inhibitors, the w3-derivatives AVX001 and AVX002, and their effects on inflammatory PGE2 production in cultures of renal mesangial cells. KEY RESULTSAVX001 and AVX002 dose-dependently inhibited the group IVA cytosolic phospholipase A2 (cPLA2) in an in vitro activity assay with similar IC50 values for AVX001 and AVX002, whereas the known cPLA2 inhibitor AACOCF3 was less potent and docosahexaenoic acid (DHA) was inactive. In renal mesangial cells, AVX001 and AVX002 suppressed IL-1b-induced PGE2 synthesis. Mechanistically, this effect occurred by a down-regulation of IL-1b-induced group IIA-sPLA2 protein expression, mRNA expression and promoter activity. A similar but less potent effect was seen with AACOCF3 and no effect was seen with DHA. As gene expression of sPLA2 is known to be regulated by the transcription factor NF-kB, we further investigated NF-kB activation. Both compounds prevented NF-kB activation by blocking degradation of the inhibitor of kB. CONCLUSIONS AND IMPLICATIONSThese data show for the first time that the novel cPLA2 inhibitors AVX001 and AVX002 exert an anti-inflammatory effect in cultures of renal mesangial cells and reduce the pro-inflammatory mediator PGE2 through an inhibitory effect on NF-kB activation. Therefore, these compounds may represent promising novel drugs for the treatment of inflammatory disorders. AbbreviationsAACOCF3, ATK, arachidonyl-trifluoromethyl ketone; AVX001, 1-octadeca-2,6,9,12,15-pentaenylsulfanyl-propan-2-one; AVX002, 1-octadeca-3,6,9,12,15-pentaenylsulfanyl-propan-2-one; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; IkB, inhibitor of kB; MAFP, methyl-arachidonyl fluorophosphonate; PAF-AH, PAF acetylhydrolase; PUFA, polyunsaturated fatty acid; RT-PCR, reverse transcriptase-PCR BJP British Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2012 British Journal of Pharmacology (2012) IntroductionMesangial cells are specialized smooth muscle-like cells located in the renal glomerulus and are not only involved in the regulation of the glomerular filtration rate and in the preservation of the structural integrity of the glomerulus, but also play a central role in most pathological processes of the renal glomerulus (Kashgarian and Sterzel, 1992;Pfeilschifter, 1994;Gómez-Guerrero et al., 2005). Upon activation by a variety of pro-inflammatory cytokines, mesangial cells respond with three prominent reactions which are all hallmarks of many forms of glomerulonephritis: (i) increased proliferation; (ii) increased mediator production, including cytokines, chemokines, NO, superoxide radicals and PGs; and (iii) increased extracellular matrix production (Kashgarian and Sterzel, 1992;Pfeilschifter, 1994). The detailed mechanisms underlying these cellular responses are still not completely understood. One importan...

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Fish Oil Decreases Macrophage Tumor Necrosis Factor Gene Transcription by Altering the NFκB Activity

Cited by 211 publications

References 37 publications

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Growth performance and immune responses in chickens after challenge with lipopolysaccharide and modulation by dietary different oils

The ω3‐polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A₂ and suppress PGE₂ formation in mesangial cells

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Fish Oil Decreases Macrophage Tumor Necrosis Factor Gene Transcription by Altering the NFκB Activity

Cited by 211 publications

References 37 publications

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Functional Heterogeneity of CD11c-positive Adipose Tissue Macrophages in Diet-induced Obese Mice

Growth performance and immune responses in chickens after challenge with lipopolysaccharide and modulation by dietary different oils

The ω3‐polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A2 and suppress PGE2 formation in mesangial cells

Contact Info

Product

Resources

About

The ω3‐polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A₂ and suppress PGE₂ formation in mesangial cells