Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells.
Proinflammatory cytokines secreted from microglia are known to induce a secondary immune response in astrocytes leading to an inflammatory loop. Cytokines also interfere with neurogenesis during aging and in neurodegenerative diseases. The present study examined the mechanism of induction of inflamm...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3726669?pdf=render |
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| author | Subbiah Pugazhenthi Yuji Zhang Ron Bouchard Gregory Mahaffey |
| author_facet | Subbiah Pugazhenthi Yuji Zhang Ron Bouchard Gregory Mahaffey |
| author_sort | Subbiah Pugazhenthi |
| collection | DOAJ |
| description | Proinflammatory cytokines secreted from microglia are known to induce a secondary immune response in astrocytes leading to an inflammatory loop. Cytokines also interfere with neurogenesis during aging and in neurodegenerative diseases. The present study examined the mechanism of induction of inflammatory mediators at the transcriptional level in human differentiated neuroprogenitor cells (NPCs). Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced the expression of cytokines and chemokines in differentiated human NPCs as shown by an immune pathway-specific array. Network motif (NM) analysis of these genes revealed 118 three-node NMs, suggesting complex interactions between inflammatory mediators and transcription factors. Immunofluorescent staining showed increases in the levels of IL-8 and CXCL10 proteins in neurons and glial cells. Findings from Taqman low density array suggested the synergistic actions of IL-1β and TNF-α in the induction of a majority of inflammatory genes by a mechanism involving NF-kB and STAT-1. Nuclear localization of these transcription factors in differentiated NPCs was observed following exposure to IL-1α and TNF-α. Further studies on CXCL10, a chemokine known to be elevated in the Alzheimer's brain, showed that TNF-α is a stronger inducer of CXCL10 promoter when compared to IL-1β. The synergy between these cytokines was lost when ISRE or kB elements in CXCL10 promoter were mutated. Our findings suggest that the activation of inflammatory pathways in neurons and astrocytes through transcription factors including NF-kB and STAT-1 play important roles in neuroglial interactions and in sustaining the vicious cycle of inflammatory response. |
| first_indexed | 2024-12-10T05:53:27Z |
| format | Article |
| id | doaj.art-751546a7e4164d49a2c6a5521ebdaa0a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T05:53:27Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-751546a7e4164d49a2c6a5521ebdaa0a2022-12-22T02:00:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6958510.1371/journal.pone.0069585Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells.Subbiah PugazhenthiYuji ZhangRon BouchardGregory MahaffeyProinflammatory cytokines secreted from microglia are known to induce a secondary immune response in astrocytes leading to an inflammatory loop. Cytokines also interfere with neurogenesis during aging and in neurodegenerative diseases. The present study examined the mechanism of induction of inflammatory mediators at the transcriptional level in human differentiated neuroprogenitor cells (NPCs). Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) induced the expression of cytokines and chemokines in differentiated human NPCs as shown by an immune pathway-specific array. Network motif (NM) analysis of these genes revealed 118 three-node NMs, suggesting complex interactions between inflammatory mediators and transcription factors. Immunofluorescent staining showed increases in the levels of IL-8 and CXCL10 proteins in neurons and glial cells. Findings from Taqman low density array suggested the synergistic actions of IL-1β and TNF-α in the induction of a majority of inflammatory genes by a mechanism involving NF-kB and STAT-1. Nuclear localization of these transcription factors in differentiated NPCs was observed following exposure to IL-1α and TNF-α. Further studies on CXCL10, a chemokine known to be elevated in the Alzheimer's brain, showed that TNF-α is a stronger inducer of CXCL10 promoter when compared to IL-1β. The synergy between these cytokines was lost when ISRE or kB elements in CXCL10 promoter were mutated. Our findings suggest that the activation of inflammatory pathways in neurons and astrocytes through transcription factors including NF-kB and STAT-1 play important roles in neuroglial interactions and in sustaining the vicious cycle of inflammatory response.http://europepmc.org/articles/PMC3726669?pdf=render |
| spellingShingle | Subbiah Pugazhenthi Yuji Zhang Ron Bouchard Gregory Mahaffey Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells. PLoS ONE |
| title | Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells. |
| title_full | Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells. |
| title_fullStr | Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells. |
| title_full_unstemmed | Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells. |
| title_short | Induction of an inflammatory loop by interleukin-1β and tumor necrosis factor-α involves NF-kB and STAT-1 in differentiated human neuroprogenitor cells. |
| title_sort | induction of an inflammatory loop by interleukin 1β and tumor necrosis factor α involves nf kb and stat 1 in differentiated human neuroprogenitor cells |
| url | http://europepmc.org/articles/PMC3726669?pdf=render |
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