Modulation of inflammatory responses by fractalkine signaling in microglia.
Reactive microglia are suggested to be involved in neurological disorders, and the mechanisms underlying microglial activity may provide insights into therapeutic strategies for neurological diseases. Microglia produce immunological responses to various stimuli, which include fractalkine (FKN or CX3...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0252118 |
| _version_ | 1818742759950909440 |
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| author | Koichi Inoue Hiroyuki Morimoto Masahiro Ohgidani Takatoshi Ueki |
| author_facet | Koichi Inoue Hiroyuki Morimoto Masahiro Ohgidani Takatoshi Ueki |
| author_sort | Koichi Inoue |
| collection | DOAJ |
| description | Reactive microglia are suggested to be involved in neurological disorders, and the mechanisms underlying microglial activity may provide insights into therapeutic strategies for neurological diseases. Microglia produce immunological responses to various stimuli, which include fractalkine (FKN or CX3CL1). CX3CR1, a FKN receptor, is present in microglial cells, and when FKN is applied before lipopolysaccharide (LPS) administration, LPS-induced inflammatory responses are inhibited, suggesting that the activation of the FKN signal is beneficial. Considering the practical administration for treatment, we investigated the influence of FKN on immunoreactive microglia using murine primary microglia and BV-2, a microglial cell line. The administration of LPS leads to nitric oxide (NO) production. NO was reduced when FKN was administered 4 h after LPS administration without a change in inducible nitric oxide synthase expression. In contrast, morphological changes, migratory activity, and proliferation were not altered by delayed FKN treatment. LPS decreases the CX3CR1 mRNA concentration, and the overexpression of CX3CR1 restores the FKN-mediated decrease in NO. CX3CR1 overexpression decreased the NO production that is mediated by LPS even without the application of FKN. ATP and ethanol also reduced CX3CR1 mRNA concentrations. In conclusion, the delayed FKN administration modified the LPS-induced microglial activation. The FKN signals were attenuated by a reduction in CX3CR1 by some inflammatory stimuli, and this modulated the inflammatory response of microglial cells, at least partially. |
| first_indexed | 2024-12-18T02:17:38Z |
| format | Article |
| id | doaj.art-cc2470ae2e0c460bb9515a695760febe |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T02:17:38Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cc2470ae2e0c460bb9515a695760febe2022-12-21T21:24:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01165e025211810.1371/journal.pone.0252118Modulation of inflammatory responses by fractalkine signaling in microglia.Koichi InoueHiroyuki MorimotoMasahiro OhgidaniTakatoshi UekiReactive microglia are suggested to be involved in neurological disorders, and the mechanisms underlying microglial activity may provide insights into therapeutic strategies for neurological diseases. Microglia produce immunological responses to various stimuli, which include fractalkine (FKN or CX3CL1). CX3CR1, a FKN receptor, is present in microglial cells, and when FKN is applied before lipopolysaccharide (LPS) administration, LPS-induced inflammatory responses are inhibited, suggesting that the activation of the FKN signal is beneficial. Considering the practical administration for treatment, we investigated the influence of FKN on immunoreactive microglia using murine primary microglia and BV-2, a microglial cell line. The administration of LPS leads to nitric oxide (NO) production. NO was reduced when FKN was administered 4 h after LPS administration without a change in inducible nitric oxide synthase expression. In contrast, morphological changes, migratory activity, and proliferation were not altered by delayed FKN treatment. LPS decreases the CX3CR1 mRNA concentration, and the overexpression of CX3CR1 restores the FKN-mediated decrease in NO. CX3CR1 overexpression decreased the NO production that is mediated by LPS even without the application of FKN. ATP and ethanol also reduced CX3CR1 mRNA concentrations. In conclusion, the delayed FKN administration modified the LPS-induced microglial activation. The FKN signals were attenuated by a reduction in CX3CR1 by some inflammatory stimuli, and this modulated the inflammatory response of microglial cells, at least partially.https://doi.org/10.1371/journal.pone.0252118 |
| spellingShingle | Koichi Inoue Hiroyuki Morimoto Masahiro Ohgidani Takatoshi Ueki Modulation of inflammatory responses by fractalkine signaling in microglia. PLoS ONE |
| title | Modulation of inflammatory responses by fractalkine signaling in microglia. |
| title_full | Modulation of inflammatory responses by fractalkine signaling in microglia. |
| title_fullStr | Modulation of inflammatory responses by fractalkine signaling in microglia. |
| title_full_unstemmed | Modulation of inflammatory responses by fractalkine signaling in microglia. |
| title_short | Modulation of inflammatory responses by fractalkine signaling in microglia. |
| title_sort | modulation of inflammatory responses by fractalkine signaling in microglia |
| url | https://doi.org/10.1371/journal.pone.0252118 |
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