IL-33 reduces the development of atherosclerosis

Miller, Ashley M.; Xu, Damo; Asquith, Darren L.; Denby, Laura; Li, Yubin; Sattar, Naveed; Baker, Andrew H.; McInnes, Iain B.; Liew, Foo Y.

doi:10.1084/jem.20071868

Cited by 581 publications

(557 citation statements)

References 31 publications

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“…IL‐33 expression has been reported in cells expressing α‐smooth muscle actin in the adventitia of atherosclerotic aortas 11. Herein, we confirm the expression of IL‐33 in the nucleus of cells in the adventitia of all groups except for IL‐33 −/− ApoE −/− mice (Fig 2, upper and middle panels).…”

Section: Resultssupporting

confidence: 81%

“…To determine whether the absence of IL‐33 or ST2 promotes a Th1 rather than a Th2 immunological profile as described 11, cytokine responses were assessed in in vitro cultivated sinus‐draining mediastinal and peripheral (including axillary and inguinal) lymph node cells. Levels of IFNγ were lower in the supernatant of mediastinal (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Coadministration of a neutralizing anti‐IL‐5 antibody with IL‐33 prevented the reduction in plaque size, indicating that IL‐5 mediated the atheroprotective effect of IL‐33. The neutralization of endogenous IL‐33 by the administration of soluble ST2, which acts as a decoy receptor for IL‐33, exacerbated the development of atherosclerotic plaques in the aortic sinus and led to increased IFNγ levels in both serum and the supernatant of in vitro‐stimulated peripheral lymph node cells 11. These data suggested that exogenously administrated IL‐33 plays a protective role in the development of atherosclerosis.…”

Section: Introductionmentioning

confidence: 93%

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Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

Martin

Palmer

Rodriguez

et al. 2015

Immunity Inflam & Disease

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Interleukin (IL)‐33 is a cytokine of the IL‐1 family, which signals through the ST2 receptor. Previous work demonstrated that the systemic administration of recombinant IL‐33 reduces the development of atherosclerosis in apolipoprotein E‐deficient (ApoE−/−) mice by inducing a Th1‐to‐Th2 shift. The objective of our study was to examine the role of endogenous IL‐33 and ST2 in atherosclerosis. ApoE−/−, IL‐33−/−ApoE−/−, and ST2−/−ApoE−/− mice were fed with a cholesterol‐rich diet for 10 weeks. Additionally, a group of ApoE−/− mice was injected with a neutralizing anti‐ST2 or an isotype control antibody during the period of the cholesterol‐rich diet. Atherosclerotic lesion development was measured by Oil Red O staining in the thoracic‐abdominal aorta and the aortic sinus. There were no significant differences in the lipid‐staining area of IL‐33−/−ApoE−/−, ST2−/−ApoE−/−, or anti‐ST2 antibody‐treated ApoE−/− mice, compared to ApoE−/− controls. The absence of IL‐33 signaling had no major and consistent impact on the Th1/Th2 cytokine responses in the supernatant of in vitro‐stimulated lymph node cells. In summary, deficiency of the endogenously produced IL‐33 and its receptor ST2 does not impact the development of atherosclerosis in ApoE‐deficient mice.

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Section: Resultssupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

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Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

Martin

Palmer

Rodriguez

et al. 2015

Immunity Inflam & Disease

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“…28 Similar to the effects of UV, IL-33 has potent immunemodulating properties that are mediated by the induction of cytokines including IL-1, -4, -6, -10. and -13, as well as chemokines such as CXCL8, CCL2, CCL3, and CCL5. 22,23,29,30 Consequently, although IL-33 can reduce the development of atheroscleoris 31 and prevent the development of parasitic-induced encephalitis, 32 it may also promote the development of asthma 33 and ar-thritis. 29 Recently, the immune-modulating functions of IL-33 have been extended to include attenuation of bacterial sepsis via neutrophil recruitment 28 and the activation of newly discovered "nuocytes" for the effective elimination of parasitic infections.…”

mentioning

confidence: 99%

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

Byrne

Beaugie

O’Sullivan

et al. 2011

The American Journal of Pathology

103

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The cellular and molecular mechanisms by which UV radiation modulates inflammation and immunity while simultaneously maintaining skin homeostasis is complex and not completely understood. Similar to the effects of UV, IL-33 has potent immune-modulating properties that are mediated by the downstream induction of cytokines and chemokines. We have discovered that exposure of mice in vivo or human skin samples ex vivo to inflammatory doses of UVB induced IL-33 expression within the epidermal and dermal skin layers. Using a combination of murine cell lines and primary human cells, we demonstrate that both UV and the oxidized lipid platelet activating factor induce IL-33 expression in keratinocytes and dermal fibroblasts. Highlighting the significance of these results, we found that administering IL-33 to mice in vivo suppressed the induction of Th1-mediated contact hypersensitivity responses. This may have consequences for skin cancer growth because UV-induced squamous cell carcinomas that evade immunological destruction were found to express significantly higher levels of IL-33. Finally, we demonstrate that dermal mast cells and skininfiltrating neutrophils closely associate with UV-induced IL-33-expressing fibroblasts. Our results therefore identify and support a role for IL-33 as an important early danger signal produced in response to inflammation-inducing UV radiation.

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“…14,27 IL-33 must be present extracellularly in order to play the crucial role in inflammatory, infectious and autoimmune diseases including anaphylactic shock, asthma, rheumatoid arthritis, atherosclerosis, systemic sclerosis and cardiovascular diseases. 5,11,[28][29][30][31][32][33][34][35][36][37][38] However, complexities and a number of discrepancies in the processing and secretion of IL-33 have been uncovered in the accumulated data. For example, full-length 31-kDa IL-33 1-270 has been reported, variously, as the immature/mature or inactive/active IL-33.…”

Section: Introductionmentioning

confidence: 99%

The enigmatic processing and secretion of interleukin-33

Zhao

2010

Cell Mol Immunol

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Interleukin-33 (IL-33) is the most attractive novel cytokine identified as an IL-1 family member. IL-33 was first named NF-HEV (nuclear factor from high endothelial venules), as it was known to interact with nuclear chromatin although its exact intracellular functions are still to be clarified. IL-33 is now recognized as the specific ligand for the orphan IL-1 receptor family member ST2 and to be involved in polarization of T cells towards T helper 2 cell phenotype and in activation of mast cells, bosophils, eosinophils and natural killer cells. It is essential for IL-33 to be extracellularly released in order to bind to the ST2 receptor and consequently play a crucial role in inflammatory, infectious and autoimmune diseases. However, like the IL-1 family members, IL-1b and IL-18, IL-33 mRNA is translated without a signal sequence for secretion. Additionally, IL-33 cannot be released by the processing and secretion mechanism shared by IL-1b and IL-18 as IL-33 is not a substrate of caspase-1 and does not require proteolysis for activation. In contrast, IL-33 can be inactivated by apoptotic caspases. Accordingly, IL-33 is proposed to be released as an alarmin from necrotic cells but to be deleted during apoptosis. Besides the known autocrine, paracrine, intracrine, juxtacrine and retrocrine mechanisms of cellular interaction with cytokines, release by necrotic cells is another pathway for a cytokine to display its function, which we suggest might be called 'necrocrine'. This mini review summarizes recent progress of how IL-33 displays potential immunoregulatory roles with a particular focus on its enigmatic production. INTRODUCTIONIn the ever-growing list of cytokines, interleukin-33 (IL-33), one of the IL-1 family members (also called IL-1F11), is a most interesting novel cytokine. This cytokine was first named in 2003 as NF-HEV (nuclear factor from high endothelial venules), as it was known to interact with nuclear chromatin in an intracrine manner. 1 It was rediscovered in 2005 as the specific extracellular ligand for the orphan IL-1 receptor family member ST2, and named IL-33. 2 ST2 (also known as IL-1RL1, DER4, T1 and FIT-1) belongs to the Toll-like/IL-1 receptor superfamily. [3][4][5] It has been well documented to be the cellular marker for differentiated T helper 2 (Th2) cells 6,7 and to be expressed on mast cells. 8,9 As a nuclear factor, the intracellular functions of IL-33 remain to be further clarified, although overexpression studies suggested a role as a transcriptional repressor. 10 As an extracellular cytokine, binding of IL-33 to the ST2 receptor activates nuclear factor-kB and mitogen-activated protein kinases, [3][4][5]11 and is involved in the polarization of T cells towards the Th2 cell phenotype 2,6,7,[11][12][13][14] and in activation of mast cells, 15-20 bosophils, 14,20-24 eosinophils, 24-26 and natural killer cells. 14,27 IL-33 must be present extracellularly in order to play the crucial role in inflammatory, infectious and autoimmune diseases including anaphylactic shock, asthma, rheum...

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IL-33 reduces the development of atherosclerosis

Cited by 581 publications

References 31 publications

Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

The enigmatic processing and secretion of interleukin-33

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