IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

Zhang, Haifeng; Wu, Maoxiong; Lin, Yongqing; Xie, Shuanglun; Huang, Tao; Liu, Pin‐Ming; Nie, Ruqiong; Meng, Q.; Luo, Na; Chen, Yangxin; Wang, Jingfeng

doi:10.1038/emm.2017.183

Cited by 29 publications

(37 citation statements)

References 30 publications

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“…The IL-33/ST2 complex thus suppresses IL-1β generation and the down-stream activation of the TLR signaling pathway by sequestration of MyD88 with the consequence of further inhibiting NF-kB and activating MAP kinases [46]. IL-33 indeed activates ERK1\2 and STAT3, facilitating binding of STAT3 to the − 1954 to − 1936 bp sequence upstream of the IL-10 transcription start site, thereby promoting its transcription in macrophages [47]. Although we did not analyze M1 and M2 monocytes in this study, previously published data indicate that M2 cells are significantly reduced in AD.…”

Section: Discussionmentioning

confidence: 99%

IL-33 and its decoy sST2 in patients with Alzheimer’s disease and mild cognitive impairment

Saresella

Marventano

Piancone

et al. 2020

J Neuroinflammation

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Background: Interleukin-33 is a cytokine endowed with pro-and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer's disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Method: IL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 on in vitro Aβ 42-stimulated monocytes of AD, MCI, and HC individuals was examined. Results: As compared to HC, (1) IL-33 was significantly decreased in serum and CSF of AD and MCI, (2) sST2 was increased in serum of AD and MCI but was undetectable in CSF, (3) serum and CSF IL-1β concentration was significantly increased and that of IL-10 was reduced in AD and MCI, whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+Aβ 42-stimulated monocytes downregulated IL-1β generation in MCI and HC, but not in AD, and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+Aβ 42-stimulated monocytes of HC alone. Conclusions: These data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD-and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI.

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Section: Discussionmentioning

confidence: 99%

IL-33 and its decoy sST2 in patients with Alzheimer’s disease and mild cognitive impairment

Saresella

Marventano

Piancone

et al. 2020

J Neuroinflammation

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“…Cytokines are a large group of peptides and proteins, which are known to be involved in the signaling between the cells of the immune system [1, 2]. Examples of cytokines include interleukins (ILs), chemokines, interferons (IFNs), colony stimulating factors, tumour necrosis factors (TNFs), transforming growth factors (TGFs) and adipokines.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory markers and bone health in postmenopausal women: a cross-sectional overview

et al. 2019

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Background Cytokines, chemokines, C-reactive proteins (CRP) and ferritin are known inflammatory markers. However, cytokines such as interleukin (IL-1β), (IL-6) and tumour necrosis factor (TNF-α) have been reported to interfere with both the bone resorption and bone formation processes. Similarly, immune cell cytokines are known to contribute to inflammation of the adipose tissue especially with obesity. IL-10 but not IL-33 has been linked to lower ferritin levels and anemia. In this study, we hypothesized that specific cytokine levels in the plasma of women with low bone mineral density (BMD) would be higher than those in the plasma of healthy women due to the actions of elevated levels of pro-inflammatory cytokines in inducing osteoclast formation and differentiation during senescence. Results Levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in the plasma of the osteoporotic group compared to the osteopenic and/or healthy groups. Meanwhile CRP levels were significantly lower in women with osteoporosis ( P = 0.040) than the osteopenic and healthy groups. Hip BMD values were significantly lower in women with high/detectable values of IL-1β ( P = 0.020) and IL-6 ( P = 0.030) compared to women where these were not detected. Similarly, women with high/detectable values of IL-1β had significantly lower spine BMD than those where IL-1β was not detected ( P = 0.030). Participants’ CRP levels were significantly positively correlated with BMI, fat mass and fat percentage ( P < 0.001). In addition, ferritin levels of women with high/detectable values of anti-osteoclastogenic IL-10 ( P = 0.012) and IL-33 ( P = 0.017) were significantly lower than those where these were not detected. There was no statistically significant association between TNF-α and BMD of the hip and lumbar spine. Conclusions High levels of cytokines (IFNα2, IFN-γ, IL-12p70, IL-33) and MCP-1 in apparently healthy postmenopausal women are associated with bone health issues. In addition, an increase in levels of IL-10 and IL-33 may be associated with low ferritin levels in this age group. Trial registration ANZCTR, ACTRN12617000802303. Registered May 31st, 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373020

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“…The requirement of the ST2 receptor in the anti-foam cell actions of IL-33 together with associated changes in gene expression was confirmed by the use of bone marrow-derived macrophages (BMDM) from mice deficient in this receptor 10 . Subsequent studies have also confirmed the requirement of the ST2 receptor in the IL-33-mediated regulation of expression of other genes in human macrophages together with its anti-foam cell action 11,13 . IL-33 also inhibited macropinocytosis 5 , which contributes to the disease via the macrophage uptake of LDL particles 1 .…”

Section: Introductionmentioning

confidence: 77%

The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways

Buckley

Williams

Chan

et al. 2019

Sci Rep

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Atherosclerosis, a chronic inflammatory disorder of the walls of arteries, causes more deaths worldwide than any other disease. Cytokines, which are present at high levels in atherosclerotic plaques, play important roles in regulating the initiation and the progression of the disease. Previous studies using animal and cell culture model systems revealed protective, anti-atherogenic effects of the cytokine interleukin-33 (IL-33). The action of this cytokine involves both the induction and suppression of expression of many genes. Unfortunately, the signaling pathways that are responsible for the inhibition of gene expression by this cytokine are poorly understood. Further studies are required given the important roles of genes whose expression is inhibited by IL-33 in key cellular processes associated with atherosclerosis such as monocyte recruitment, foam cell formation and lipoprotein metabolism. We have investigated here the roles of various known IL-33 activated signaling pathways in such inhibitory actions using RNA interference-mediated knockdown assays and monocyte chemotactic protein-1 and intercellular adhesion molecule-1 as model genes. Key roles were identified for extracellular signal-regulated kinase-1/2, p38α kinase, c-Jun N-terminal kinase-1/2, phosphoinositide 3-kinase-γ, and p50 and p65 nuclear factor-κB in such inhibitory action of IL-33. These studies provide new insights on the signaling pathways through which IL-33 inhibits the macrophage expression of key atherosclerosis-associated genes.

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IL-33 promotes IL-10 production in macrophages: a role for IL-33 in macrophage foam cell formation

Cited by 29 publications

References 30 publications

IL-33 and its decoy sST2 in patients with Alzheimer’s disease and mild cognitive impairment

IL-33 and its decoy sST2 in patients with Alzheimer’s disease and mild cognitive impairment

Inflammatory markers and bone health in postmenopausal women: a cross-sectional overview

The interleukin-33-mediated inhibition of expression of two key genes implicated in atherosclerosis in human macrophages requires MAP kinase, phosphoinositide 3-kinase and nuclear factor-κB signaling pathways

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