IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture
Tyler C Moore,1 Terrence Scott Pinkerton,1 Thomas M Petro2 1Department of Biology, College of Science and Technology, Bellevue University, Bellevue, NE, 68005, USA; 2Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, 68583, USACorrespondence: Thomas M Petro, Department o...
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Dove Medical Press
2025-01-01
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| Series: | Journal of Inflammation Research |
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| author | Moore TC Pinkerton TS Petro TM |
| author_facet | Moore TC Pinkerton TS Petro TM |
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| description | Tyler C Moore,1 Terrence Scott Pinkerton,1 Thomas M Petro2 1Department of Biology, College of Science and Technology, Bellevue University, Bellevue, NE, 68005, USA; 2Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, 68583, USACorrespondence: Thomas M Petro, Department of Oral Biology, University of Nebraska Medical Center, College of Dentistry, 4000 East Campus Loop South, Lincoln, NE, 68583, USA, Email tpetro@unmc.eduIntroduction: Macrophage responses to lipopolysaccharides (LPS) drive inflammatory diseases, such as periodontitis, with production of IL-6 and Nitric Oxide (NO). However, anti-inflammatory macrophages counter inflammation with the production of CCL22. Interferon regulatory factor 3 (IRF3) plays a significant role in expression of both IL-6 and NO during macrophage responses through Interferon-stimulated Response Elements (ISREs) of promoters.Methods: To determine the role of IRF3 in LPS-induced pro- and anti-inflammatory macrophage responses, we used the macrophage cell line RAW264.7 modified with an ISRE promoter driving secreted luciferase (RAW264.7-Lucia) to assess IRF3 activity in response to Escherichia coli and Porphyromonas gingivalis LPS. For comparison, responses to poly I:C and IFN-gamma and responses from RAW264.7 cells deficient in IRF3 were also assessed.Results: Herein, LPS of P. gingivalis, significantly enhanced production of IL-6 and NO that was induced by E. coli LPS but significantly decreased poly I:C-induced ISRE promoter activity. Moreover, IRF3 deficiency depressed the LPS-induced ISRE promoter activity and NO production but increased IL-6 and CCL22 in response to LPS. Restoration of IRF3 expression in IRF3KO RAW cells increased IL-6, restored NO, and decreased CCL22 production in response to LPS of E. coli.Discussion: Therefore, IRF3 is critical to the expression of pro- and anti-inflammatory factors produced by macrophages responding to LPS and could be a target during periodontitis treatment.Keywords: IRF3, lipopolysaccharide, macrophages, RAW264.7 cells, cytokines |
| format | Article |
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| institution | Kabale University |
| issn | 1178-7031 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Journal of Inflammation Research |
| spelling | doaj-art-0fbda34f37284b99918e1c052b550fdf2025-01-27T18:05:33ZengDove Medical PressJournal of Inflammation Research1178-70312025-01-01Volume 181255126599645IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in CultureMoore TCPinkerton TSPetro TMTyler C Moore,1 Terrence Scott Pinkerton,1 Thomas M Petro2 1Department of Biology, College of Science and Technology, Bellevue University, Bellevue, NE, 68005, USA; 2Department of Oral Biology, University of Nebraska Medical Center, Lincoln, NE, 68583, USACorrespondence: Thomas M Petro, Department of Oral Biology, University of Nebraska Medical Center, College of Dentistry, 4000 East Campus Loop South, Lincoln, NE, 68583, USA, Email tpetro@unmc.eduIntroduction: Macrophage responses to lipopolysaccharides (LPS) drive inflammatory diseases, such as periodontitis, with production of IL-6 and Nitric Oxide (NO). However, anti-inflammatory macrophages counter inflammation with the production of CCL22. Interferon regulatory factor 3 (IRF3) plays a significant role in expression of both IL-6 and NO during macrophage responses through Interferon-stimulated Response Elements (ISREs) of promoters.Methods: To determine the role of IRF3 in LPS-induced pro- and anti-inflammatory macrophage responses, we used the macrophage cell line RAW264.7 modified with an ISRE promoter driving secreted luciferase (RAW264.7-Lucia) to assess IRF3 activity in response to Escherichia coli and Porphyromonas gingivalis LPS. For comparison, responses to poly I:C and IFN-gamma and responses from RAW264.7 cells deficient in IRF3 were also assessed.Results: Herein, LPS of P. gingivalis, significantly enhanced production of IL-6 and NO that was induced by E. coli LPS but significantly decreased poly I:C-induced ISRE promoter activity. Moreover, IRF3 deficiency depressed the LPS-induced ISRE promoter activity and NO production but increased IL-6 and CCL22 in response to LPS. Restoration of IRF3 expression in IRF3KO RAW cells increased IL-6, restored NO, and decreased CCL22 production in response to LPS of E. coli.Discussion: Therefore, IRF3 is critical to the expression of pro- and anti-inflammatory factors produced by macrophages responding to LPS and could be a target during periodontitis treatment.Keywords: IRF3, lipopolysaccharide, macrophages, RAW264.7 cells, cytokineshttps://www.dovepress.com/irf3-promotes-production-of-il-6-and-nitric-oxide-but-represses-ccl22--peer-reviewed-fulltext-article-JIRirf3lipopolysaccharidemacrophagesraw264.7 cellscytokines |
| spellingShingle | Moore TC Pinkerton TS Petro TM IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture Journal of Inflammation Research irf3 lipopolysaccharide macrophages raw264.7 cells cytokines |
| title | IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture |
| title_full | IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture |
| title_fullStr | IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture |
| title_full_unstemmed | IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture |
| title_short | IRF3 Promotes Production of IL-6 and Nitric Oxide but Represses CCL22 in RAW264.7 Macrophage Cells Exposed to Lipopolysaccharides in Culture |
| title_sort | irf3 promotes production of il 6 and nitric oxide but represses ccl22 in raw264 7 macrophage cells exposed to lipopolysaccharides in culture |
| topic | irf3 lipopolysaccharide macrophages raw264.7 cells cytokines |
| url | https://www.dovepress.com/irf3-promotes-production-of-il-6-and-nitric-oxide-but-represses-ccl22--peer-reviewed-fulltext-article-JIR |
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