New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes
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. Th...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2549 |
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| author | Dong Young Kang Nipin Sp Eun Seong Jo Jin-Moo Lee Kyoung-Jin Jang |
| author_facet | Dong Young Kang Nipin Sp Eun Seong Jo Jin-Moo Lee Kyoung-Jin Jang |
| author_sort | Dong Young Kang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T06:39:47Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:47Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-ad942833a6f24f44801db0ba4ade9a522023-11-22T17:45:24ZengMDPI AGCells2073-44092021-09-011010254910.3390/cells10102549New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human MonocytesDong Young Kang0Nipin Sp1Eun Seong Jo2Jin-Moo Lee3Kyoung-Jin Jang4Department of Pathology, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Chungju 27478, KoreaDepartment of Pathology, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Chungju 27478, KoreaPharmacological Research Division, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Cheongju-si 28159, KoreaPharmacological Research Division, National Institute of Food and Drug Safety Evaluation, Osong Health Technology Administration Complex, Cheongju-si 28159, KoreaDepartment of Pathology, Institute of Biomedical Science and Technology, School of Medicine, Konkuk University, Chungju 27478, KoreaIron 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.https://www.mdpi.com/2073-4409/10/10/2549iron metabolismheme biosynthesisLPShigh glucoseinflammatory responseTLR4/NF-κB |
| spellingShingle | Dong Young Kang Nipin Sp Eun Seong Jo Jin-Moo Lee Kyoung-Jin Jang New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes Cells iron metabolism heme biosynthesis LPS high glucose inflammatory response TLR4/NF-κB |
| title | New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes |
| title_full | New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes |
| title_fullStr | New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes |
| title_full_unstemmed | New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes |
| title_short | New Insights into the Pivotal Role of Iron/Heme Metabolism in TLR4/NF-κB Signaling-Mediated Inflammatory Responses in Human Monocytes |
| title_sort | new insights into the pivotal role of iron heme metabolism in tlr4 nf κb signaling mediated inflammatory responses in human monocytes |
| topic | iron metabolism heme biosynthesis LPS high glucose inflammatory response TLR4/NF-κB |
| url | https://www.mdpi.com/2073-4409/10/10/2549 |
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