Towards a role of interleukin-32 in atherosclerosis

Heinhuis, Bas; Popa, Călin; Tits, Berry L.J.H. van; Kim, Soohyun; Zeeuwen, Patrick L.J.M.; Berg, Wim B. van den; Meer, J.W.M. van der; Vliet, J. Adam van der; Stalenhoef, Anton F. H.; Dinarello, Charles A.; Netea, Mihai G.; Joosten, Leo A. B.

doi:10.1016/j.cyto.2013.05.002

Cited by 41 publications

(47 citation statements)

References 29 publications

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“…IL-32 promotes angiogenesis propagating vascular inflammation and exacerbates sepsis in a mouse model [36, 37]. Recent studies have shown that atherosclerosis maybe associated with IL-32 production [38]. …”

Section: Discussionmentioning

confidence: 99%

Scropolioside B Inhibits IL-1βand Cytokines Expression through NF-κB and Inflammasome NLRP3 Pathways

Zhu

Zhang

Ling

et al. 2014

Mediators of Inflammation

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Chronic inflammation is associated with various chronic illnesses including immunity disorders, cancer, neurodegeneration, and vascular diseases. Iridoids are compounds with anti-inflammatory properties. However their anti-inflammatory mechanism remains unclear. Here, we report that scropolioside B, isolated from a Tibetan medicine (Scrophularia dentata Royle ex Benth.), blocked expressions of TNF, IL-1, and IL-32 through NF-κB pathway. Scropolioside B inhibited NF-κB activity in a dose-dependent manner with IC50 values of 1.02 μmol/L. However, catalpol, similar to scropolioside B, was not effective in inhibiting NF-κB activity. Interestingly, scropolioside B and catalpol decreased the expression of NLRP3 and cardiolipin synthetase at both the mRNA and protein level. Our results showed that scropolioside B is superior in inhibiting the expression, maturation, and secretion of IL-1β compared to catalpol. These observations provide further understanding of the anti-inflammatory effects of iridoids and highlight scropolioside B as a potential drug for the treatment of rheumatoid arthritis and atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Scropolioside B Inhibits IL-1βand Cytokines Expression through NF-κB and Inflammasome NLRP3 Pathways

Zhu

Zhang

Ling

et al. 2014

Mediators of Inflammation

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“…Diluted cDNA was used for qPCR analysis that was done by using the StepOnePlus sequence detection systems (Applied Biosystems, Foster City, CA, USA) with SYBR Green Mastermix (Applied Biosystems). Primer sequences (S2 Table) for IL-32 were previously developed by [3,40] whereas other primer sequences (TNFα, IL-1β, IL-8, IL-1Ra, IL-10, inducible nitric oxide synthase [iNOS], cathelicidin, b-defensin) were obtained from Harvard Primerbank database. Primers were purchased from Biolegio.…”

Section: Methodsmentioning

confidence: 99%

Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species

et al. 2017

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BackgroundInterleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown.Methodology/Principal findingsIn the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) braziliensis or L. (Leishmania) amazonensis to investigate the role of IL-32 in infection. We report that Leishmania species induces IL-32γ, and show that intracellular IL-32γ protein production is dependent on endogenous TNFα. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFα and IL-8. Remarkably, the infection index was augmented in the absence of IL-32 and decreased in cells overexpressing this cytokine. Mechanistically, these effects can be explained by nitric oxide cathelicidin and β-defensin 2 production regulated by IL-32.ConclusionsThus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites.

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“…A detailed analysis of local vascular inflammation and cytokine expression in atherosclerotic plaques revealed that a balance between pro-inflammatory cytokines—such as interleukin (IL)-1, IL-2, IL-12, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α—and anti-inflammatory cytokines—such as IL-4, IL-5, IL-10, and IL-13—is crucial for lesion development 12. IL-32 has also been implicated as a critical regulator of EC function and vascular inflammation 13-16; therefore, it is likely to participate in the development of atherosclerosis. IL-32 is reportedly involved in the pathogenesis of chronic diseases including rheumatoid arthritis, inflammatory bowel disease, Alzheimer's disease, cancer, and diabetes 17-23.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-32α Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis

et al. 2017

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Interleukin-32 (IL-32) is a multifaceted cytokine that promotes inflammation and regulates vascular endothelial cell behavior. Although some IL-32 isoforms have been reported to contribute to vascular inflammation and atherosclerosis, the functional role of IL-32α in vascular inflammation and atherogenesis has not been studied.Methods: IL-32α function was assessed in cells with transient IL-32α overexpression or treated with recombinant human IL-32α by western blotting and mRNA expression analysis. Vascular smooth muscle cell (VSMC) proliferation and migration was examined by BrdU incorporation and wound healing assays, respectively. In addition, the participation of IL-32α on vascular inflammation, arterial wall thickening, and atherosclerosis in vivo was monitored in human IL-32α transgenic (hIL-32α-Tg) mice with or without ApoE knockout (ApoE-/-/hIL-32α-Tg).Results: Our analyses showed that IL-32α suppresses genes involved in the inflammatory and immune responses and cell proliferation, and by limiting matrix metalloproteinase (MMP) function. In vivo, administration of hIL-32α inhibited vascular inflammation and atherosclerosis in hIL-32α-Tg and ApoE-/-/hIL-32α-Tg mice. Subsequent microarray and in silico analysis also revealed a marked decreased in inflammatory gene expression in hIL-32α-Tg mice. Collectively, our studies demonstrated that IL-32α upregulates the atheroprotective genes Timp3 and Reck by downregulating microRNA-205 through regulation of the Rprd2-Dgcr8/Ddx5-Dicer1 biogenesis pathway.Conclusion: Our findings provide the first direct evidence that IL-32α is an anti-inflammatory and anti-atherogenic cytokine that may be useful as a diagnostic and therapeutic protein in atherosclerosis.

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Towards a role of interleukin-32 in atherosclerosis

Cited by 41 publications

References 29 publications

Scropolioside B Inhibits IL-1βand Cytokines Expression through NF-κB and Inflammasome NLRP3 Pathways

Scropolioside B Inhibits IL-1βand Cytokines Expression through NF-κB and Inflammasome NLRP3 Pathways

Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species

Interleukin-32α Inhibits Endothelial Inflammation, Vascular Smooth Muscle Cell Activation, and Atherosclerosis by Upregulating Timp3 and Reck through suppressing microRNA-205 Biogenesis

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