Immunomodulatory effects of statins and autoimmune rheumatic diseases: Novel intracellular mechanism involved

Tristano, Antonio G.; Fuller, Kathy

doi:10.1016/j.intimp.2006.08.006

Cited by 23 publications

(16 citation statements)

References 153 publications

(201 reference statements)

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“…[76]]. In concordance with that, Pakozdi et al [77] found that MIF induces RA-FLSs matrix metaloproteinases (MMPs)-2 expression in a time-dependent and concentration-dependent manner, and this required the protein kinase C (PKC), c-jun N-terminal kinase (JNK), and Src signalling pathways.…”

Section: Fibroblast and Pdgfrsupporting

confidence: 57%

“…In concordance with that, Pakozdi et al [77] found that MIF induces RA-FLSs matrix metaloproteinases (MMPs)-2 expression in a time-dependent and concentration-dependent manner, and this required the protein kinase C (PKC), c-jun N-terminal kinase (JNK), and Src signalling pathways. Moreover, it has been demonstrated that inhibition of MAPK pathways, including p38 MAPK, ERK-1/2, and JNK in different cells from RA patients, prevented the expression of RANKL, the production of MMPs and cytokines, and cartilage destruction [76]. Finally, Morel et al [78] examined the signal transduction mechanisms by which IL-8 induces VCAM-1 expression in RA-FLSs.…”

Section: Fibroblast and Pdgfrmentioning

confidence: 99%

“…The cells involved in this complication have been extensively studied and although the mechanisms of cartilage destruction in RA were well described; the specific mechanisms responsible for bone erosion in this disease have only recently been studied [76]. Recent studies have shown that osteoclasts are involved in the pathogenesis of bone and joint destruction and can be a potent therapeutic target of this disease.…”

Section: Osteoclast C-fms and C-srcmentioning

confidence: 99%

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Tyrosine kinases as targets in rheumatoid arthritis

Tristano

2009

International Immunopharmacology

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Section: Fibroblast and Pdgfrsupporting

confidence: 57%

Section: Fibroblast and Pdgfrmentioning

confidence: 99%

Section: Osteoclast C-fms and C-srcmentioning

confidence: 99%

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Tyrosine kinases as targets in rheumatoid arthritis

Tristano

2009

International Immunopharmacology

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“…These studied further suggest that Treg numbers and functions may be influenced by statins. 34,35) In this study, we found that statin therapy of humans with ACS increased the number and function of circulating nTregs, enhanced the FOXP3 mRNA transcript levels and FOXP3 protein expression, and augmented the suppressive properties of Tregs in vivo as a whole. It is currently poorly understood how atorvastatin treatment influences both Treg numbers as well as FOXP3 gene expression.…”

Section: Discussionmentioning

confidence: 62%

Changes of Naturally Occurring CD4+CD25+ FOXP3+ Regulatory T Cells in Patients With Acute Coronary Syndrome and the Beneficial Effects of Atorvastatin Treatment

Wang¹,

Wang

Li³

et al. 2015

Int. Heart J.

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SummaryTo determine the number and function of naturally occurring CD4+ regulatory T cells (nTregs) in patients with acute coronary syndrome (ACS) and to determine the effects of a low dose of atorvastatin treatment (20 mg/day) on nTregs.Patients with ACS were randomly divided into a group receiving conventional therapy (n = 60) or conventional therapy supplemented with atorvastatin (20 mg/day) (n = 60). A group of healthy volunteers that did not suffer from ACS was used as controls (n = 60). T lymphocytes were isolated from ACS patients, both before and 4 weeks after treatment, or control patients and the percentage of nTregs was determined by flow cytometry. Serum levels of cytokines were determined by enzyme-linked immunosorbent assays. A mixed lymphocyte reaction was used to determine the ability of nTregs to inhibit proliferation of effector T cells. Quantitative PCR and Western blot were used to analyze (forkhead box P3) FOXP3 mRNA transcript levels and the expression of FOXP3 protein.In ACS patients, the percentage and inhibitory properties of nTregs were reduced, IFN-γ and hsCRP levels were increased, and IL-10 and TGF-β 1 levels were lowered. Atorvastatin treatment increased the percentage and inhibitory ability of nTregs, decreased serum IFN-γ and hsCRP levels, and decreased IL-10 and TGF-β 1 levels, as compared with the non-atorvastatin group.Our findings suggest that nTregs play an atheroprotective role in atherosclerosis. The inhibitory effects of atorvastatin on inflammation in ACS may be due to its beneficial effects on nTregs and restoration of immune homeostasis. (Int Heart J 2015; 56: 163-169)

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“…Those effects are partly due to the interference with the mevalonate pathway and inhibition of geranylgeranylation and prenylation of guanine nucleotide-binding proteins (GTPases) 17. However, their cellular and molecular mechanisms of action are not yet fully understood.…”

mentioning

confidence: 99%