Inhibition of Arthritis in the Lewis Rat by Apolipoprotein A-I and Reconstituted High-Density Lipoproteins

Wu, Ben J.; Shrestha, Sudichhya; Chen, Kang; Tabet, Fatiha; Barter, Philip J.; Rye, Kerry‐Anne

doi:10.1161/atvbaha.113.302832

Cited by 36 publications

(35 citation statements)

References 38 publications

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“…Our data demonstrate that rHDL's anti-inflammatory effects on LPS-stimulated BMDCs are mediated through interference with the MyD88/NF-κB pathway. Although the inhibitory actions of apoA-I and HDL on TLR signaling have been previously reported (19, 54), a mechanism by which HDL selectively impedes the MyD88-dependent signaling in DCs has not yet been established. Based on our findings we speculate that interaction of apoA-I on HDL with cell surface lipid transporters such as ABCA1 or SR-BI, leads to changes in downstream signaling events that in turn compromise NF-κB activation and transcriptional upregulation of Myd88 by LPS.…”

Section: Discussionmentioning

confidence: 99%

“…Particularly, treatment of rats with an apoA-I mimetic peptide inhibited collagen-induced arthritis and reduced inflammatory cytokine levels (18). Moreover, administration of apoA-I or rHDL attenuated peptidoglycan-polysaccharide (PG-PS)-induced arthritis in Lewis female rats in an ABCA1-dependent manner (19). Although HDL modulates the activity of various immune cell subsets (12), the mechanism through which HDL regulates autoreactive T cell responses in vivo remains elusive.…”

Section: Introductionmentioning

confidence: 99%

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High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

Tiniakou

Δράκος

Sinatkas

et al. 2015

The Journal of Immunology

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Aberrant levels and function of the potent anti-inflammatory high-density lipoprotein (HDL) and accelerated atherosclerosis have been reported in patients with autoimmune inflammatory diseases. Whether HDL affects the development of an autoimmune response remains elusive. Herein, we utilized apolipoprotein A-I deficient (apoA-I-/-) mice, characterized by diminished circulating HDL levels, to delineate the role of HDL in autoimmunity. ApoA-I-/-mice exhibited increased severity of antigen-induced arthritis compared to wild-type mice and this was associated with elevated Th1 and Th17 cell reactivity in the draining lymph nodes (dLNs). Furthermore, reconstituted HDL (rHDL) attenuated IFN-γ and IL-17 secretion by antigen-specific T cells upon stimulation of dLNs in vitro. The suppressive effects of rHDL were mediated through modulation of dendritic cell (DC) function. Specifically, rHDL-treated DCs demonstrated an immature phenotype characterized by downregulated co-stimulatory molecules, the release of low amounts of pro-inflammatory cytokines, and failure to promote T cell proliferation in vitro. The mechanism of action involved the inhibition of NF-κB nuclear translocation and the decrease of Myd88 mRNA levels by rHDL. Finally, modulation of DC function by rHDL was critically dependent on the presence of SR-BIand ABCA1 but not of the ABCG1 transporter. These findings reveal a novel role of HDL in the regulation of adaptive inflammatory responses through suppression of DC function that could be exploited therapeutically in autoimmune inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

Tiniakou

Δράκος

Sinatkas

et al. 2015

The Journal of Immunology

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“…It is well known that PGPS can up-regulate TLR2 expression, which enhances inflammatory responses against infection (Komori et al, 2011; Wu et al, 2014). The enhanced inflammatory responses are involved in many factors, including inflammatory regulators and mucin during the development of OM (Han et al, 2009a; Han et al, 2009b; Roy et al, 2014; Trune and Zheng, 2009).…”

Section: Resultsmentioning

confidence: 99%

“…This protocol causes most Tlr2 −/− mice death within three days (Han et al, 2009a), making it difficult to observe the long-term effect of OM. Peptidoglycan-polysaccharide (PGPS) of the bacterial cell wall can induce inflammation against bacterial infection by up-regulating TLR2 expression (Komori et al, 2011) and cause acute and chronic arthritis (Esser et al, 1985; Stimpson et al, 1987; Wu et al, 2014). Previous studies have shown that after clearance of Gram+ bacterial infection in the middle ears (MEs) by immune system, bacterial PGPS may be persistent in the MEs, causing COM (Fulghum and Brown, 1998; Komori et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2−/−) mice for developing drug therapy

Zhang

Zheng

Sang

et al. 2015

Infection, Genetics and Evolution

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Background Toll like receptor 2 (TLR2) signaling can regulate the pathogenesis of otitis media (OM). However, the precise role of TLR2 signaling in OM has not been clarified due to the lack of an optimal animal model. Peptidoglycan-polysaccharide (PGPS) of the bacterial cell wall can induce inflammation by activating the TLR2 signaling. This study aimed at examining the pathogenic characteristics of OM induced by PGPS in Tlr2−/− mice, and the potential therapeutic effect of Sodium aescinate (SA) in this model. Methods Wild-type (WT) and Tlr2−/− mice were inoculated with streptococcal PGPS into their middle ears (MEs) and treated intravenously with vehicle or SA daily beginning at 3 days prior to PGPS for 6 consecutive days. The pathologic changes of individual mice were evaluated longitudinally. Results In comparison with WT mice, Tlr2−/− mice were susceptible to PGPS-induced OM. Tlr2−/− mice displayed greater hearing loss, tympanic membrane damage, ME mucosal thickening, longer inflammation state, cilia and goblet cell loss. SA-treatment decreased neutrophil infiltration, modulated TLR2-related gene expression and improved ciliary organization. Conclusions PGPS induced a relatively stable OM in Tlr2−/− mice, providing a new model for OM research. Treatment with SA mitigated the pathogenic damage in the ME and may be valuable for intervention of OM.

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“…ApoA-I and reconstituted HDL have been shown to reduce inflammatory tissue injury by multiple mechanisms (128). As discussed in this review, HDL-associated proteins and lipids reduce I/R injury by preserving mitochondrial function.…”

Section: Discussionmentioning

confidence: 99%

High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms

White

Giordano

Anantharamaiah

2016

Chemistry and Physics of Lipids

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Ischemic injury is associated with acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting and open heart surgery. The timely re-establishment of blood flow is critical in order to minimize cardiac complications. Reperfusion after a prolonged ischemic period, however, can induce severe cardiomyocyte dysfunction with mitochondria serving as a major target of ischemia/reperfusion (I/R) injury. An increase in the formation of reactive oxygen species (ROS) induces damage to mitochondrial respiratory complexes leading to uncoupling of oxidative phosphorylation. Mitochondrial membrane perturbations also contribute to calcium overload, opening of the mitochondrial permeability transition pore (mPTP) and the release of apoptotic mediators into the cytoplasm. Clinical and experimental studies show that ischemic preconditioning (ICPRE) and postconditioning (ICPOST) attenuate mitochondrial injury and improve cardiac function in the context of I/R injury. This is achieved by the activation of two principal cell survival cascades: 1) the Reperfusion Injury Salvage Kinase (RISK) pathway; and 2) the Survivor Activating Factor Enhancement (SAFE) pathway. Recent data suggest that high density lipoprotein (HDL) mimics the effects of conditioning protocols and attenuates myocardial I/R injury via activation of the RISK and SAFE signaling cascades. In this review, we discuss the roles of apolipoproteinA-I (apoA-I), the major protein constituent of HDL, and sphingosine 1-phosphate (S1P), a lysosphingolipid associated with small, dense HDL particles as mediators of cardiomyocyte survival. Both apoA-I and S1P exert an infarct-sparing effect by preventing ROS-dependent injury and inhibiting the opening of the mPTP.

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Inhibition of Arthritis in the Lewis Rat by Apolipoprotein A-I and Reconstituted High-Density Lipoproteins

Cited by 36 publications

References 38 publications

High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

High-Density Lipoprotein Attenuates Th1 and Th17 Autoimmune Responses by Modulating Dendritic Cell Maturation and Function

Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2−/−) mice for developing drug therapy

High-density lipoprotein, mitochondrial dysfunction and cell survival mechanisms

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