Carbon monoxide blocks lipopolysaccharide-induced gene expression by interfering with proximal TLR4 to NF-kappaB signal transduction in human monocytes
Carbon monoxide (CO) is an endogenous messenger that suppresses inflammation, modulates apoptosis and promotes vascular remodeling. Here, microarrays were employed to globally characterize the CO (250 ppm) suppression of early (1 h) LPS-induced inflammation in human monocytic THP-1 cells. CO suppressed 79 of 101 immediate-early genes induced by LPS; 19% (15/79) were transcription factors and most others were cytokines, chemokines and immune response genes. The prototypic effects of CO on transcription and protein production occurred early but decreased rapidly. CO activated p38 MAPK, ERK1/2 and Akt and caused an early and transitory delay in LPS-induced JNK activation. However, selective inhibitors of these kinases failed to block CO suppression of LPS-induced IL-1beta, an inflammation marker. Of CO-suppressed genes, 81% (64/79) were found to have promoters with putative NF-kappaB binding sites. CO was subsequently shown to block LPS-induced phosphorylation and degradation of IkappaBalpha in human monocytes, thereby inhibiting NF-kappaB signal transduction. CO broadly suppresses the initial inflammatory response of human monocytes to LPS by reshaping proximal events in TLR4 signal transduction such as stress kinase responses and early NF-kappaB activation. These rapid, but transient effects of CO may have therapeutic applications in acute pulmonary and vascular injury.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2009 |
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| Erschienen: |
2009 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
PloS one - 4(2009), 12 vom: 02. Dez., Seite e8139 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chhikara, Maneesha [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 17.03.2010 Date Revised 20.10.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0008139 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM193230631 |
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| 100 | 1 | |a Chhikara, Maneesha |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Carbon monoxide blocks lipopolysaccharide-induced gene expression by interfering with proximal TLR4 to NF-kappaB signal transduction in human monocytes |
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| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Carbon monoxide (CO) is an endogenous messenger that suppresses inflammation, modulates apoptosis and promotes vascular remodeling. Here, microarrays were employed to globally characterize the CO (250 ppm) suppression of early (1 h) LPS-induced inflammation in human monocytic THP-1 cells. CO suppressed 79 of 101 immediate-early genes induced by LPS; 19% (15/79) were transcription factors and most others were cytokines, chemokines and immune response genes. The prototypic effects of CO on transcription and protein production occurred early but decreased rapidly. CO activated p38 MAPK, ERK1/2 and Akt and caused an early and transitory delay in LPS-induced JNK activation. However, selective inhibitors of these kinases failed to block CO suppression of LPS-induced IL-1beta, an inflammation marker. Of CO-suppressed genes, 81% (64/79) were found to have promoters with putative NF-kappaB binding sites. CO was subsequently shown to block LPS-induced phosphorylation and degradation of IkappaBalpha in human monocytes, thereby inhibiting NF-kappaB signal transduction. CO broadly suppresses the initial inflammatory response of human monocytes to LPS by reshaping proximal events in TLR4 signal transduction such as stress kinase responses and early NF-kappaB activation. These rapid, but transient effects of CO may have therapeutic applications in acute pulmonary and vascular injury | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Intramural | |
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| 700 | 1 | |a Wang, Shuibang |e verfasserin |4 aut | |
| 700 | 1 | |a Kern, Steven J |e verfasserin |4 aut | |
| 700 | 1 | |a Ferreyra, Gabriela A |e verfasserin |4 aut | |
| 700 | 1 | |a Barb, Jennifer J |e verfasserin |4 aut | |
| 700 | 1 | |a Munson, Peter J |e verfasserin |4 aut | |
| 700 | 1 | |a Danner, Robert L |e verfasserin |4 aut | |
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