TLR-4 agonistic lipopolysaccharide upregulates interleukin-8 at the transcriptional and post-translational level in vascular smooth muscle cells

Hong, Taek-Jong; Ban, Ji Eun; Choi, Kyung-Ha; Son, Yonghae; Kim, Sunmi; Eo, Seong-Kug; Park, Hee-Ju; Rhim, Byung Yong; Kim, Koanhoi

doi:10.1016/j.vph.2008.08.006

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…The resveratrol-related enhancement of the human iNOS and IL-8 promoter activity might be explained by the resveratrol-dependent increase of NF-κB and/or STAT-1α activity (see Supplementary Figure S1D and E). As shown in rat mesangial cells (59), A7r5 rat aortic smooth muscle cells (54) and murine RAW macrophages (53), the reduced iNOS, IL-8 or TNF-α expression in human DLD-1 cells after resveratrol treatment cannot be explained only by impaired promoter activity. In contrast, Chung et al.…”

Section: Discussionmentioning

confidence: 88%

Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity

Bollmann

Art

Henke

et al. 2014

Nucleic Acids Research

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Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-α mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol.

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Section: Discussionmentioning

confidence: 88%

Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity

Bollmann

Art

Henke

et al. 2014

Nucleic Acids Research

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“…Expression of TLR4 on human vascular SMCs at the protein level has been shown [93, 94] and more importantly, functional expression of TLRs on smooth muscle cells has also been described. Exposure of aortic SMCs to the TLR4 agonist LPS induces MCP-1, IL6 and IL-8 production [91, 94, 95]. Stimulation of SMCs with the synthetic dsRNA ligand Poly:IC results in MCP1 and IL6 release [90] and exposure of SMCs to Chlamydia pneumoniae leads to TLR2-dependent MCP-1 release [92].…”

Section: Expression Of Toll-like Receptorsmentioning

confidence: 99%

The Expression and Functions of Toll-Like Receptors in Atherosclerosis

Cole¹,

Georgiou²,

Monaco³

2010

Mediators of Inflammation

146

101

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Inflammation drives atherosclerosis. Both immune and resident vascular cell types are involved in the development of atherosclerotic lesions. The phenotype and function of these cells are key in determining the development of lesions. Toll-like receptors are the most characterised innate immune receptors and are responsible for the recognition of exogenous conserved motifs on pathogens, and, potentially, some endogenous molecules. Both endogenous and exogenous TLR agonists may be present in atherosclerotic plaques. Engagement of toll-like receptors on immune and resident vascular cells can affect atherogenesis as signalling downstream of these receptors can elicit proinflammatory cytokine release, lipid uptake, and foam cell formation and activate cells of the adaptive immune system. In this paper, we will describe the expression of TLRs on immune and resident vascular cells, highlight the TLR ligands that may act through TLRs on these cells, and discuss the consequences of TLR activation in atherosclerosis.

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“…LPS also induces the expression of IL-6, IL-1 and IFN-mRNAs prior to increases in ADRP, which in turn stimulate expression of ADRP. Similarly exposure of aortic smooth muscle cells to LPS which is agonistic to TLR-4 resulted in induction of IL-8 gene transcription via promoter activation as well as enhanced release of IL-8 protein [9]. This was inhibited by the dietary antioxidant curcumin, which has implications in reducing inflammatory loading generated by cardiovascular and periodontal diseases.…”

Section: Introductionmentioning

confidence: 99%

Redox Status in Periodontal and Systemic Inflammatory Conditions Including Associated Neoplasias: Antioxidants as Adjunctive Therapy?

Soory

2009

IDDT

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The aetiopathogenesis of periodontal diseases is initiated by microbial biofilm which could lead to a hyperinflammatory status in aggressive forms of the disease; and cause an imbalance in the redox status, resulting in oxidative stress-induced damage. There is increasing documentation of the link between periodontal and other inflammatory diseases driven by a pro-oxidant profile. This could impose a significant systemic loading of reactive oxygen species relevant to metabolic, arthritic, age related and neoplastic diseases. They demonstrate similar markers of risk / oxidative stress induced injury during disease progression which abate in response to treatment. In certain aggressive forms of periodontal diseases resulting in a substantial systemic pro-oxidant profile, the co-existence of systemic diseases with a similar inflammatory pathogenesis could lead to progressive tissue / organ damage fuelled by the same process. Some of the common mechanisms involved are discussed, relevant to periodontal, metabolic and rheumatoid diseases, pregnancy and the foetus, age related changes and certain neoplasias which have been recently linked to periodontal disease progression. In view of a distinct pro-oxidant profile in severe cases there may a role for selective use of antioxidant adjuncts with suitable therapeutic targeting. It is relevant that periodontal diseases are associated with the above diseases and a small but significant overall cancer risk which persists in non-smokers. Periodontal disease may be a useful marker of a susceptible immune system, or directly affect the progression of systemic diseases due to inflammatory loading. Formulation of therapeutic agents shown to have efficacy in this context, with accurate targeting is a challenge.

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TLR-4 agonistic lipopolysaccharide upregulates interleukin-8 at the transcriptional and post-translational level in vascular smooth muscle cells

Cited by 12 publications

References 30 publications

Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity

Resveratrol post-transcriptionally regulates pro-inflammatory gene expression via regulation of KSRP RNA binding activity

The Expression and Functions of Toll-Like Receptors in Atherosclerosis

Redox Status in Periodontal and Systemic Inflammatory Conditions Including Associated Neoplasias: Antioxidants as Adjunctive Therapy?

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