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Article

New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes

1
Department of Pathology, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Chungju 27478, Korea
2
Pharmacological Research Division, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Cheongju-si 28159, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Academic Editor: Saghi Ghaffari
Cells 2021, 10(10), 2549; https://doi.org/10.3390/cells10102549
Received: 23 July 2021 / Revised: 23 September 2021 / Accepted: 24 September 2021 / Published: 27 September 2021
(This article belongs to the Special Issue Mitochondrial Damage and Dysfunction in Immunology)
Iron metabolism and heme biosynthesis are essential processes in cells during the energy cycle. Alteration in these processes could create an inflammatory condition, which results in tumorigenesis. Studies are conducted on the exact role of iron/heme metabolism in induced inflammatory conditions. This study used lipopolysaccharide (LPS)- or high-glucose-induced inflammation conditions in THP-1 cells to study how iron/heme metabolism participates in inflammatory responses. Here, we used iron and heme assays for measuring total iron and heme. We also used flow cytometry and Western blotting to analyze molecular responses. Our results demonstrated that adding LPS or high-glucose induced iron formation and heme synthesis and elevated the expression levels of proteins responsible for iron metabolism and heme synthesis. We then found that further addition of heme or 5-aminolevulinic acid (ALA) increased heme biosynthesis and promoted inflammatory responses by upregulating TLR4/NF-κB and inflammatory cytokine expressions. We also demonstrated the inhibition of heme synthesis using succinylacetone (SA). Moreover, N-MMP inhibited LPS- or high-glucose-induced inflammatory responses by inhibiting TLR4/NF-κB signaling. Hence, iron/heme metabolism checkpoints could be considered a target for treating inflammatory conditions. View Full-Text
Keywords: iron metabolism; heme biosynthesis; LPS; high glucose; inflammatory response; TLR4/NF-κB iron metabolism; heme biosynthesis; LPS; high glucose; inflammatory response; TLR4/NF-κB
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MDPI and ACS Style

Kang, D.Y.; Sp, N.; Jo, E.S.; Lee, J.-M.; Jang, K.-J. New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes. Cells 2021, 10, 2549. https://doi.org/10.3390/cells10102549

AMA Style

Kang DY, Sp N, Jo ES, Lee J-M, Jang K-J. New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes. Cells. 2021; 10(10):2549. https://doi.org/10.3390/cells10102549

Chicago/Turabian Style

Kang, Dong Y., Nipin Sp, Eun S. Jo, Jin-Moo Lee, and Kyoung-Jin Jang. 2021. "New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes" Cells 10, no. 10: 2549. https://doi.org/10.3390/cells10102549

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