Interleukin-1 receptor type-1 in non-hematopoietic cells is the target for the pro-atherogenic effects of interleukin-1 in apoE-deficient mice

Shemesh, Shay; Kamari, Yehuda; Shaish, Aviv; Olteanu, Sarita; Kandel-Kfir, Michal; Almog, Tal; Grosskopf, Itamar; Apte, Ron N.; Harats, Dror

doi:10.1016/j.atherosclerosis.2011.12.010

Cited by 41 publications

(24 citation statements)

References 28 publications

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“…The mutual induction of IL-1α and IL-1β has been previously documented (14,53,54). We recently showed that IL-1α deficiency results in reduced expression of IL-1β in macrophages (55,56) and in the liver (57). Importantly, IL-1β-KO mice revealed a more subtle but a similar phenotype of reproductive advantage as seen in IL-1α-KO mice.…”

Section: Discussionmentioning

confidence: 76%

Interleukin-1 deficiency prolongs ovarian lifespan in mice

Uri-Belapolsky

Shaish

Eliyahu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proinflammatory cytokine IL-1 in the age-related exhaustion of ovarian reserve using IL-1α and IL-1β-KO mice. IL-1α-KO mice showed a substantially higher pregnancy rate and litter size compared with WT mice at advanced age. The number of secondary and antral follicles was significantly higher in 2.5-mo-old IL-1α-KO ovaries compared with WT ovaries. Serum anti-Müllerian hormone, a putative marker of ovarian reserve, was markedly higher in IL-1α-KO mice from 2.5 mo onward, along with a greater ovarian response to gonadotropins. IL-1β-KO mice displayed a comparable but more subtle prolongation of ovarian lifespan compared with IL-1α-KO mice. The protein and mRNA of both IL-1α and IL-1β mice were localized within the developing follicles (oocytes and granulosa cells), and their ovarian mRNA levels increased with age. Molecular analysis revealed decreased apoptotic signaling [higher B-cell lymphoma 2 (BCL-2) and lower BCL-2-associated X protein levels], along with a marked attenuation in the expression of genes coding for the proinflammatory cytokines IL-1β, IL-6, and TNF-α in ovaries of IL-1α-KO mice compared with WT mice. Taken together, IL-1 emerges as an important participant in the age-related exhaustion of ovarian reserve in mice, possibly by enhancing the expression of inflammatory genes and promoting apoptotic pathways.

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Section: Discussionmentioning

confidence: 76%

Interleukin-1 deficiency prolongs ovarian lifespan in mice

Uri-Belapolsky

Shaish

Eliyahu

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, TLR-1/2, TLR-4 or TLR-9-stimulated (without a second stimulus) macrophages from IL-1a-deficient mice had specifically lower IL-1b mRNA and protein levels compared to WT macrophages [10]. Reports that macrophages [27] and dendritic cells [10] from IL-1R1-deficient mice do not produce lower levels of IL-1b compared to WT mice, provided further support that IL-1a may regulate the expression of IL-1b in mouse macrophages through an intracrine pathway independent of IL-1R1. Although IL-1a associates with chromatin, it does not contain a DNA binding domain and was therefore presumed to be part of a protein complex that binds to DNA to affect transcription indirectly.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of interleukin-1α does not attenuate LPS-induced production of interleukin-1β in mouse macrophages

et al. 2015

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“…Included gingivitis in model to promote atherosclerosis (918). Most important site is EC (875,1610). Less marked effects reported previously without gingivitis (270).…”

Section: Il-1r1 Il-1r1mentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

379

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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Interleukin-1 receptor type-1 in non-hematopoietic cells is the target for the pro-atherogenic effects of interleukin-1 in apoE-deficient mice

Cited by 41 publications

References 28 publications

Interleukin-1 deficiency prolongs ovarian lifespan in mice

Interleukin-1 deficiency prolongs ovarian lifespan in mice

Knockdown of interleukin-1α does not attenuate LPS-induced production of interleukin-1β in mouse macrophages

Molecular Biology of Atherosclerosis

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