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| Status |
Public on May 01, 2023 |
| Title |
Nicotinamide regulates LPS-induced HIF-1alpha responses through post-translational modifications in human macrophages |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Mechanisms to control the immune response are important to pathogen evasion and host defense. Gram-negative bacteria are common pathogens that can activate host immune responses through their outer membrane component, lipopolysaccharide (LPS). Macrophages activated by LPS induce cell signals that promote hypoxic metabolism, phagocytosis, and antigen presentation. Nicotinamide (NAM) is a vitamin B3 derivative and precursor in the formation of nicotinamide adenine dinucleotide (NAD), which is a required co-factor in cellular function. In this study, treatment of human monocyte derived macrophages with NAM antagonized LPS-induced responses by altering the expression of ubiquitin genes, increasing HIF-1alpha and p65/RelA ubiquitination, decreasing p65/RelA acetylation and promoting the formation of the proteasome. NAM also elevated intracellular NAD levels and altered the genetic expression of sirtuins and poly(ADP-ribose) polymerases. These NAM responses highlight post-translational events in regulating the host response to pathogens and identify the ubiquitome as a target in pathogen evasion and host defense.
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| Overall design |
Each of the four male donor human monocyte-derived macrophages (HMDMs) were treated with four conditions for four hours. The conditions included vehicle control, 10ng/ml lipopolysaccharide (LPS), 10mM nicotinamide (NAM), or LPS plus NAM. There were 16 total samples: 4 control, 4 LPS, 4 NAM, and 4 LPS+NAM.
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| Contributor(s) |
Curran CS, Dougherty EJ, Demirkale CY, Torabi-Parizi P |
| Citation(s) |
37314413 |
| Submission date |
Nov 04, 2021 |
| Last update date |
Sep 11, 2023 |
| Contact name |
abdel elkahloun |
| E-mail(s) |
abdel@mail.nih.gov
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| Organization name |
nih
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| Street address |
50 south dr
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| City |
bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
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| Samples (16)
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| Relations |
| BioProject |
PRJNA777918 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE188206_RAW.tar |
37.4 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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