CEACAM1 promotes vascular aging processes

Kleefeldt, Florian; Rueckschloss, Uwe; Ergün, Süleyman

doi:10.18632/aging.102868

Cited by 6 publications

(2 citation statements)

References 8 publications

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“…Furthermore, CEACAM1 deficiency enhanced the permeability of tumor vasculature due to increased basal Akt kinase and endothelial nitric oxide synthase (eNOS) activities (120). This is in line with the concept that CEACAM1 is required for the establishment of the endothelial barrier (121,122). Besides endothelial cells CEACAM1 expression in myeloid cells also promoted angiogenesis as shown by bone marrow transplantation experiments in mice (123).…”

Section: Angiogenesissupporting

confidence: 88%

The role of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer

Götz,

Rueckschloss,

Balk

et al. 2023

Front. Immunol.

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The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. CEACAM1 was shown to be a prognostic marker in patients suffering from cancer. In this review, we summarize pre-clinical and clinical evidence linking CEACAM1 to tumorigenicity and cancer progression. Furthermore, we discuss potential CEACAM1-based mechanisms that may affect cancer biology.

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Section: Angiogenesissupporting

confidence: 88%

The role of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer

Götz,

Rueckschloss,

Balk

et al. 2023

Front. Immunol.

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“…IL-21 receptor (IL21R) promotes inflammation in myocardial infarction [ 108 ] and respiratory disease [ 109 ]. CEACAM1 is a coronavirus receptor on endothelial cells as we reported [ 54 ] and promotes vascular aging process [ 110 ]. L1CAM regulates microRNAs associated with inflammation and progression of Alzheimer's disease and Parkinson's disease [ 111 ].…”

Section: Resultsmentioning

confidence: 99%

Procaspase-1 patrolled to the nucleus of proatherogenic lipid LPC-activated human aortic endothelial cells induces ROS promoter CYP1B1 and strong inflammation

Lu¹,

Nanayakkara²,

Sun³

et al. 2021

Redox Biology

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To determine the roles of nuclear localization of pro-caspase-1 in human aortic endothelial cells (HAECs) activated by proatherogenic lipid lysophosphatidylcholine (LPC), we examined cytosolic and nuclear localization of pro-caspase-1, identified nuclear export signal (NES) in pro-caspase-1 and sequenced RNAs. We made the following findings: 1) LPC increases nuclear localization of procaspase-1 in HAECs. 2) Nuclear pro-caspase-1 exports back to the cytosol, which is facilitated by a leptomycin B-inhibited mechanism. 3) Increased nuclear localization of pro-caspase-1 by a new NES peptide inhibitor upregulates inflammatory genes in oxidative stress and Th17 pathways; and SUMO activator N106 enhances nuclear localization of pro-caspase-1 and caspase-1 activation (p20) in the nucleus. 4) LPC plus caspase-1 enzymatic inhibitor upregulates inflammatory genes with hypercytokinemia/hyperchemokinemia and interferon pathways, suggesting a novel capsase-1 enzyme-independent inflammatory mechanism. 5) LPC in combination with NES inhibitor and caspase-1 inhibitor upregulate inflammatory gene expression that regulate Th17 activation, endotheli-1 signaling, p38-, and ERK- MAPK pathways. To examine two hallmarks of endothelial activation such as secretomes and membrane protein signaling, LPC plus NES inhibitor upregulate 57 canonical secretomic genes and 76 exosome secretomic genes, respectively, promoting four pathways including Th17, IL-17 promoted cytokines, interferon signaling and cholesterol biosynthesis. LPC with NES inhibitor also promote inflammation via upregulating ROS promoter CYP1B1 and 11 clusters of differentiation (CD) membrane protein pathways. Mechanistically, all the LPC plus NES inhibitor-induced genes are significantly downregulated in CYP1B1-deficient microarray, suggesting that nuclear caspase-1-induced CYP1B1 promotes strong inflammation. These transcriptomic results provide novel insights on the roles of nuclear caspase-1 in sensing DAMPs, inducing ROS promoter CYP1B1 and in regulating a large number of genes that mediate HAEC activation and inflammation. These findings will lead to future development of novel therapeutics for cardiovascular diseases (CVD), inflammations, infections, transplantation, autoimmune disease and cancers. (total words: 284).

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