Clonal senescence alters endothelial ICAM-1 function

Zhou, Xuebing; Perez, Felipe P.; Han, Kai; Jurivich, Donald A.

doi:10.1016/j.mad.2006.07.003

Cited by 33 publications

(25 citation statements)

References 16 publications

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“…previous reports (Burke-Gaffney and Hellewell 1996; Zhou et al 2006). This suggests that there is little difference in the TNF-a concentration most effective for inducing VCAM-1 and ICAM-1 production and membrane expression between lymphatic endothelium and blood endothelium.…”

Section: Comparison Of Tnf-a Effects On Leukocyte Adhesionsupporting

confidence: 52%

Effects of TNF-α on Leukocyte Adhesion Molecule Expressions in Cultured Human Lymphatic Endothelium

Sawa

Sugimoto

Ueki

et al. 2007

J Histochem Cytochem.

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S U M M A R Y TNF-a alters leukocyte adhesion molecule expression of cultured endothelial cells like human umbilical vein endothelial cells (HUVEC). This study was designed to investigate the changes in vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and platelet endothelial cell adhesion molecule-1 (PECAM-1) expression with TNF-a stimulation in cultured human neonatal dermal lymphatic endothelial cells (HNDLEC). The real-time quantitative PCR analysis on HNDLEC showed that TNF-a treatment leads to increases of VCAM-1 and ICAM-1 mRNAs to the 10.8-and 48.2-fold levels of untreated cells and leads to a reduction of PECAM-1 mRNA to the 0.42-fold level of untreated cells. Western blot and immunohistochemical analysis showed that TNF-a leads to VCAM-1 and ICAM-1 expressions that were inhibited by antiserum to human TNF receptor or by AP-1 inhibitor nobiletin. In flow cytometry analysis, the number of VCAM-1-and ICAM-1-positive cells increased, and PECAM-1-positive cells decreased with TNF-a treatment. Regarding protein amounts produced in cells and amounts expressed on the cell surface, VCAM-1 and ICAM-1 increased in HNDLEC and HUVEC, and PECAM-1 decreased in HNDLEC in a TNF-a concentration-dependent manner. VCAM-1, ICAM-1, and PECAM-1 protein amounts in TNFa-stimulated cells were lower in HNDLEC than in HUVEC. This suggests that the lymphatic endothelium has the TNF-a-induced signaling pathway, resulting in increased VCAM-1 and ICAM-1 expression to a weaker extent than blood endothelium and PECAM-1 reduction to a stronger extent than blood endothelium. (J Histochem Cytochem 55:721-733, 2007)

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Section: Comparison Of Tnf-a Effects On Leukocyte Adhesionsupporting

confidence: 52%

Effects of TNF-α on Leukocyte Adhesion Molecule Expressions in Cultured Human Lymphatic Endothelium

Sawa

Sugimoto

Ueki

et al. 2007

J Histochem Cytochem.

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“…LPS presensitization also induced strong expression of endothelial ICAM1 and the microglial aMb2 integrin. Both molecules subserve cell adhesion; however, they are also strongly involved in phagocytosis and inside-out signaling, 31,68,69 and, for the aMb2 integrin, have been shown to enhance neonatal neural cell death, via the superoxide ion pathway. 70 In the case of the TNF cluster of cytokines, exogenous TNFa has been shown to exacerbate focal ischemic injury and blocking endogenous TNFa has been shown to be neuroprotective.…”

Section: Discussionmentioning

confidence: 99%

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult

Kendall

Hirstova

Horn

et al. 2011

Laboratory Investigation

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In the current study, we explored the role of TNF cluster cytokines on the lipopolysaccharide (LPS)-mediated, synergistic increase in brain injury after hypoxic ischemic insult in postnatal day 7 mice. Pretreatment with moderate doses of LPS (0.3 mg/g) resulted in particularly pronounced synergistic injury within 12 h. Systemic application of LPS alone resulted in a strong upregulation of inflammation-associated cytokines TNFa, LTb, interleukin (IL) 1b, IL6, chemokines, such as CXCL1, and adhesion molecules E-Selectin, P-Selectin and intercellular adhesion molecule-1 (ICAM1), as well as a trend toward increased LTa levels in day 7 mouse forebrain. In addition, it was also associated with strong activation of brain blood vessel endothelia and local microglial cells. Here, deletion of the entire TNF gene cluster, removing TNFa, LTb and LTa completely abolished endotoxin-mediated increase in the volume of cerebral infarct. Interestingly, the same deletion also prevented endothelial and microglial activation following application of LPS alone, suggesting the involvement of these cell types in bringing about the LPS-mediated sensitization to neonatal brain injury. KEYWORDS: encephalopathy; hypoxia; inflammation; ischemia; neonate; TNF Although bacteria and viruses can directly infect and injure developing brain, infections occurring outside the brain frequently will also have a damaging effect. Congenital infections appear to contribute up to 5% of cerebral palsy cases 1,2 and may sensitize the brain to perinatal hypoxic ischemic (HI) insult. [3][4][5] This synergistic effect was also reproduced in mammalian and avian animal models, combining HI insult and the lipopolysaccharide break-down product of bacteria in HI animal models.6-10 However, the molecular mediators of this endotoxin effect in vivo are currently still unknown.Both in vitro and in vivo studies show that endotoxin will upregulate numerous cytokines and chemokines, 11 upregulate signaling enzymes, such as inducible nitrogen oxide synthase (iNOS), and cyclo-oxygenase-2 (COX2) and enhance the expression of adhesion molecules on parenchymal microglia and the brain vascular endothelium. 12-15Follow on molecular studies reveal that these effects are transmitted through the classical endotoxin receptors, primarily the toll-like receptor 4 (TLR4), on blood vessel endothelia and microglia, 16,17 and involve MyD88 and NF-kappa-B components of the innate immunity cascade. 17In particular, endotoxin-induced pro-inflammatory cytokines, including TNFa and interleukin 1b (IL1b) are known to have a number of deleterious effects, including a direct toxic effect on neurones and vulnerable oligodendrocyte precursors, 18,19 astrogliosis with release of nitric oxide, and mitochondrial dysfunction, 20 as well as microglial activation with release of nitric oxide, superoxide and a panel of other inflammation-associated molecules.

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“…In some cases, loss of proliferation-competent cells may be responsible for pathology, as in glaucoma 84 , cataracts 6 , the diabetic pancreas 58 and osteoarthritis 85 . In others, inflammation from the SASP may play a causal role in disease, as in atherosclerosis 86 , diabetic fat 58,59 and cancer 87 . Finally, SASP-mediated extracellular matrix remodeling may be key to disease progression or inhibition, as senescent cells drive pulmonary fibrosis 88 but restrict liver fibrosis 89 .…”

Section: Senescence In Age-related Diseasementioning

confidence: 99%

Cellular senescence in aging and age-related disease: from mechanisms to therapy

Childs

Durik

Baker

et al. 2015

Nat Med

1,750

1,489

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Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senescence in cultured cells has been acquired over the past half century; however, senescence in living organisms is poorly understood, largely because of technical limitations relating to the identification and characterization of senescent cells in tissues and organs. Furthermore, newly recognized beneficial signaling functions of senescence suggest that indiscriminately targeting senescent cells or modulating their secretome for anti-aging therapy may have negative consequences. Here we discuss current progress and challenges in understanding the stressors that induce senescence in vivo, the cell types that are prone to senesce, and the autocrine and paracrine properties of senescent cells in the contexts of aging and age-related diseases as well as disease therapy.

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Clonal senescence alters endothelial ICAM-1 function

Cited by 33 publications

References 16 publications

Effects of TNF-α on Leukocyte Adhesion Molecule Expressions in Cultured Human Lymphatic Endothelium

Effects of TNF-α on Leukocyte Adhesion Molecule Expressions in Cultured Human Lymphatic Endothelium

TNF gene cluster deletion abolishes lipopolysaccharide-mediated sensitization of the neonatal brain to hypoxic ischemic insult

Cellular senescence in aging and age-related disease: from mechanisms to therapy

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