PPARα activator fenofibrate modulates angiotensin II-induced inflammatory responses in vascular smooth muscle cells via the TLR4-dependent signaling pathway

Ji, Yuanyuan; Liu, Juntian; Liu, Na; Wang, Zhidong; Liu, Chuanhao

doi:10.1016/j.bcp.2009.06.095

Cited by 36 publications

(29 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current study, fenofibrate decreased LPS-induced generations of IL-18 and TIMP-1 in VSMCs, further supporting a potential role of PPARα activation in the retard of vascular inflammation. Additionally, the present results seem to be consistent with our previous findings showing that LPS leads to downregulation of PPARα and PPARγ [24], however, treatment with fenofibrate evidently antagonized LPS-reduced PPARα expression, but showed little effect on PPARγ expression in VSMCs. Consequently, PPARα agonist fenofibrate may have a direct effect on inflammation through its ability to modulate inflammatory cytokines production by VSMCs.…”

Section: Discussionsupporting

confidence: 82%

“…Quantitative real-time PCR and RT-PCR mRNA levels were determined by our previous method [24]. Total RNA was isolated using a TRIzol Kit (Invitrogen Corp., Carlsbad, CA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…As described previously [24], protein samples (20 µg) were separated on 12% SDS-PAGE gels and transferred onto a polyvinylidene difluoride (PVDF) membrane (Bio-Rad Laboratories Inc., Hercules, CA, USA). The membranes were blocked with 5% nonfat dry milk in Tris-buffered saline containing 0.1% Tween 20, and incubated with specific antibodies against TLR4 (1:200), TIMP-1 (1:400), PPARα (1:100), PPARγ (1:400), TRIF (1:600), phospho-IRF3 (1:500), IP-10 (1:5000), and β-actin (1:400).…”

Section: Western Blot Analysismentioning

confidence: 99%

See 2 more Smart Citations

Modulation of LPS-mediated Inflammation by Fenofibrate via the TRIF-dependent TLR4 Signaling Pathway in Vascular Smooth Muscle Cells

Wang²,

Li³

et al. 2010

Cell Physiol Biochem

View full text Add to dashboard Cite

Lipopolysaccharide (LPS) induced-vascular inflammation plays a central role in vasculitis and atherosclerosis. The stimulation of toll-like receptor 4 (TLR4) by LPS elicits the release of major proinflammatory cytokines that aggravates cardiovascular disorders. Peroxisome proliferator- activated receptor Α (PPARΑ) agonists have been shown to reduce cardiovascular events by controlling lipid metabolism as well as inflammation. However, the role of PPARΑ agonist fenofibrate in modulating LPS-mediated inflammatory responses in vascular smooth muscle cells (VSMCs) remains elusive. The present study demonstrated that fenofibrate exerted a potent anti-inflammatory action through reducing interleckin-1(IL-18), tissue inhibitor of metalloproteinase-1(TIMP-1), TLR4 and enhancing PPARΑ in LPS-stimulated VSMCs. Additionally, treatment of VSMCs with the TLR4 inhibition or TLR4 small-interfering RNA illustrated that the modulatory effects of fenofibrate on LPS-mediated inflammatory responses in VSMCs were reliant on TLR4. Especially, the results suggested that beneficial effects of fenofibrate on LPS-stimulated inflammatory responses in VSMCs were mediated through interference of TLR4 and its downstream signaling components such as Toll-interleckin-1(IL-1) receptor domain- containing adaptor inducing interferon-Β (TRIF), interferon regulatory factor 3 (IRF3) and interferon-gamma inducible protein 10 (IP-10). In conclusion, PPARΑ agonist fenofibrate exerts anti-inflammatory property by antagonizing LPS-mediated inflammatory responses in VSMCs. More importantly, the modulation of the TRIF-dependent signaling pathway (TLR4/TRIF/IRF3/IP-10) might be a useful and novel anti-inflammatory strategy of fenofibrate.

show abstract

Section: Discussionsupporting

confidence: 82%

“…Quantitative real-time PCR and RT-PCR mRNA levels were determined by our previous method [24]. Total RNA was isolated using a TRIzol Kit (Invitrogen Corp., Carlsbad, CA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

See 1 more Smart Citation

Modulation of LPS-mediated Inflammation by Fenofibrate via the TRIF-dependent TLR4 Signaling Pathway in Vascular Smooth Muscle Cells

Wang²,

Li³

et al. 2010

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…One of its members, TLR4, a pattern-recognizing receptor, recognizes exogenous ligands like LPS of bacterial cell wall components and activates inflammatory and innate immune responses, and then initiates intracellular signaling cascade. The TLR4 signaling can lead to activation of MAPKs, which, in turn, activates nuclear translocation of NF-B and finally initiates proinflammatory responses (Ji et al, 2009;Li et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of dichloromethane fraction from Orostachys japonicus in RAW 264.7 cells: Suppression of NF-κB activation and MAPK signaling

Lee

Ryu

Lee

et al. 2012

Journal of Ethnopharmacology

View full text Add to dashboard Cite

“…Finally, activators of PPARa limit the production of pro-atherogenic Th1 cytokines such as IFNc, TNFa, and IL-2 (Marx et al 2004) and inhibit the inflammatory response in hepatocytes by decreasing IL-1-induced CRP and IL-6-induced fibrinogen a, b, and serum amyloid A expression (Zambon et al 2006). Finally, fenofibrate-induced activation of PPARa is able to counterregulate vascular inflammation induced by Angiotensin II (Ji et al 2009). Thus PPARa acts as an antiatherogenic factor by modulating local and systemic inflammatory responses, in addition to its action on lipid homeostasis.…”

Section: Drugsmentioning

confidence: 97%

Targeting inflammation to slow or delay functional decline: where are we?

et al. 2010

View full text Add to dashboard Cite

The role of inflammation in the pathophysiology of chronic age-related diseases is increasingly recognized, and inflammation could represent the common pathway linking diseases and disability. Thus, targeting inflammation could represent a useful strategy at preventing or delaying functional decline. In this paper we review recent evidence suggesting that selected drugs, such as statins, fibrates, angiotensin converting enzyme-inhibitors and angiotensin receptor blockers, and physical exercise may be able to contrast functional decline by blunting inflammation. Results from randomized trials investigating the effects of physical activity programs on inflammation and functional decline is still limited, and further investigations are warranted.

show abstract

PPARα activator fenofibrate modulates angiotensin II-induced inflammatory responses in vascular smooth muscle cells via the TLR4-dependent signaling pathway

Cited by 36 publications

References 43 publications

Modulation of LPS-mediated Inflammation by Fenofibrate via the TRIF-dependent TLR4 Signaling Pathway in Vascular Smooth Muscle Cells

Modulation of LPS-mediated Inflammation by Fenofibrate via the TRIF-dependent TLR4 Signaling Pathway in Vascular Smooth Muscle Cells

Anti-inflammatory effects of dichloromethane fraction from Orostachys japonicus in RAW 264.7 cells: Suppression of NF-κB activation and MAPK signaling

Targeting inflammation to slow or delay functional decline: where are we?

Contact Info

Product

Resources

About