Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway

Chen, SF; Kapturczak, Matthias H.; Wasserfall, Clive; Glushakova, Olena; Campbell-Thompson, Martha; Deshane, Jessy; Joseph, R; Cruz, Pedro; Hauswirth, William W.; Madsen, Kirsten; Croker, Byron P.; Berns, Kenneth I.; Atkinson, Mark A.; Flotte, Terence R.; Tisher, C. Craig; Agarwal, Anupam

doi:10.1073/pnas.0502407102

Cited by 102 publications

(95 citation statements)

References 57 publications

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“…Consistent with previous studies (3,15,16,42), we have found that IL-10 plays a protective role in the alterations of vascular reactivity. Regional differences in cytokine-induced release and responsiveness to mediators appear to contribute to the dilator or constrictor responses observed in a specific vascular bed (42).…”

Section: Discussionsupporting

confidence: 81%

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Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

Giachini¹,

Zemse²,

Carneiro³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Section: Discussionsupporting

confidence: 81%

“…Exogenous IL-10 prevents proliferative vasculopathy by inhibiting inflammatory cell infiltration, smooth muscle cell proliferation, and chemokine expression (3,27). This cytokine counteracts the endothelial dysfunction induced by angiotensin II, lipopolysaccharide, and endothelin (ET)-1 (15,16,49,50).…”

mentioning

confidence: 99%

Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

Giachini¹,

Zemse²,

Carneiro³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…9,11 Briefly, formalin-fixed tissue from descending thoracic aorta were embedded in paraffin and cut at 5-mm thickness and mounted on superfrost plus glass slides, deparaffinized and rehydrated. Sections were blocked with normal serum and incubated overnight with primary antibody at 4 1C.…”

Section: Analysis Of Protein By Immunohistochemistrymentioning

confidence: 99%

“…For example, general immune suppressors interleukin-10 and tumor growth factor-b1 have been shown to inhibit atherosclerosis in mouse models. [8][9][10][11] The manipulation of the immune system may be achieved through cytokines or other genes that selectively inhibit T-helper cell type 1 response or other arms of the immune system, or to increase CD4(+), CD25(+) regulatory T cells (Tregs). 12,13 Atherogenesis has also been inhibited by altering lipid transport by the delivery of apolipoprotein E or apolipoprotein A1 Milano.…”

Section: Introductionmentioning

confidence: 99%

Systemic human Netrin-1 gene delivery by adeno-associated virus type 8 alters leukocyte accumulation and atherogenesis in vivo

et al. 2010

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Atherosclerosis is an inflammatory disorder of arteries. Atherosclerotic plaque, in its early to intermediate stages, is composed largely of lipid-engorged foam cells. These foam cells are derived from the trafficking of monocytes (Mo) into the arterial intima, attracted to the site by chemoattractants. Given that foam cells are derived from the trafficking of Mo, the use of Netrin-1, an Mo chemorepellent, may be useful in limiting Mo accumulation and subsequent plaque formation. To investigate the potential of Netrin-1 for limiting atherosclerosis, we systemically delivered its human (h) cDNA by adeno-associated virus type 8 (AAV8, single-stranded structure) delivery into low-density lipoprotein receptor knockout (LDLRÀ/À) mice and placed the animals on a high cholesterol diet (HCD). Compared with control neomycin resistance (Neo) gene delivery/HCD, hNetrin-1 delivery resulted in a significant reduction in plaque formation, as determined by larger aortic lumen size, thinner intima-media thickness and lower blood velocity than the Neo/HCD control (all statistically significant). Indices of monocyte/macrophage (Mo/MF) accumulation, CD68, integrin, alpha M (ITGAM) and egf-like module containing, mucin-like, hormone receptor-like 1 (EMR-1), were reduced in hNetrin-1/HCD-treated animal's aortas and spleens compared with Neo/HCD-treated animals. Unexpectedly, CD25 and foxp3 (regulatory T cells (Tregs)) in the aorta were strongly upregulated. This is the first time the Mo/MF chemorepellent approach, and specific Netrin-1 gene delivery, has been performed for the reduction of Mo/MF burden and atherosclerosis. In addition, Netrin-1 has never before been linked to altered Treg levels. These data strongly suggest that hNetrin-1 gene delivery can reduce Mo/MF accumulation, inflammation and subsequent plaque formation.

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“…Chen and colleagues found that a single intramuscular injection of an adeno-associated viral vector encoding IL-10 in recipient rats bearing abdominal aortic allografts protected the grafts from neointimal proliferation. Inhibition of HO activity with zinc protoporphyrin IX (ZnPP) abrogated the protection (40). Blocking HO activity with tin protoporphyrin IX (SnPP) also abrogates or reduces the protective effects of IL-10 in septic shock (95) and ethanol toxicity (50).…”

Section: Mp Ho-1 In Tissue Homeostasismentioning

confidence: 99%

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

Hull

Agarwal

George

2014

Antioxidants & Redox Signaling

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Significance: Heme oxygenase-1 (HO-1) is a potential therapeutic target in many diseases, especially those mediated by oxidative stress and inflammation. HO-1 expression appears to regulate the homeostatic activity and distribution of mononuclear phagocytes ( MP) in lymphoid tissue under physiological conditions. It also regulates the ability of MP to modulate the inflammatory response to tissue injury. Recent Advances: The induction of HO-1 within MP-particularly macrophages and dendritic cells-modulates the effector functions that they acquire after activation. These effector functions include cytokine production, surface receptor expression, maturation state, and polarization toward a pro-or anti-inflammatory phenotype. The importance of HO-1 in MP is emphasized by their expression of specific receptors that primarily function to ingest heme-containing substrate and deliver it to HO-1. Critical Issues: MP are the first immunological responders to tissue damage. They critically affect the outcome of injury to many organ systems, yet few therapies are currently available to specifically target MP during disease pathogenesis. Elucidation of the role of HO-1 expression in MP may help to direct broadly applicable therapies to clinical use that are based on the immunomodulatory capabilities of HO-1. Future Directions: Unraveling the complexities of HO-1 expression specifically within MP will more completely define how HO-1 provides cytoprotection in vivo. The use of models in which HO-1 expression is specifically modulated in bone marrow-derived cells will allow for a more complete characterization of its immunoregulatory properties.

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Interleukin 10 attenuates neointimal proliferation and inflammation in aortic allografts by a heme oxygenase-dependent pathway

Cited by 102 publications

References 57 publications

Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

Interleukin-10 attenuates vascular responses to endothelin-1 via effects on ERK1/2-dependent pathway

Systemic human Netrin-1 gene delivery by adeno-associated virus type 8 alters leukocyte accumulation and atherogenesis in vivo

The Mononuclear Phagocyte System in Homeostasis and Disease: A Role for Heme Oxygenase-1

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