Dorzolamide suppresses PKCδ -TIRAP-p38 MAPK signaling axis to dampen the inflammatory response
Background: Sepsis is a syndrome due to microbial infection causing impaired multiorgan function. Its underlying cause is immune dysfunction and macrophages play an essential role. Methods: TIRAP interaction with PKCδ in macrophage was studied, revealing downstream signaling by Western blot and quantitative reverse transcriptase PCR. Dorzolamide (DZD) disrupting TIRAP-PKCδ interaction was identified by virtual screening and validated in vitro and in septic mice. Results: The study highlights the indispensable role of TIRAP-PKCδ in p38 MAPK-activation, NF-κB- and AP-1-mediated proinflammatory cytokines expression, whereas DZD significantly attenuated the signaling. Conclusion: Targeting TIRAP-PKCδ interaction by DZD is a novel therapeutic approach for treating sepsis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Future medicinal chemistry - (2023) vom: 27. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rajpoot, Sajjan [VerfasserIn] |
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| Links: |
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| Themen: |
AP1 |
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| Anmerkungen: |
Date Revised 02.05.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.4155/fmc-2022-0260 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356323676 |
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| 100 | 1 | |a Rajpoot, Sajjan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dorzolamide suppresses PKCδ -TIRAP-p38 MAPK signaling axis to dampen the inflammatory response |
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| 500 | |a Date Revised 02.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a Background: Sepsis is a syndrome due to microbial infection causing impaired multiorgan function. Its underlying cause is immune dysfunction and macrophages play an essential role. Methods: TIRAP interaction with PKCδ in macrophage was studied, revealing downstream signaling by Western blot and quantitative reverse transcriptase PCR. Dorzolamide (DZD) disrupting TIRAP-PKCδ interaction was identified by virtual screening and validated in vitro and in septic mice. Results: The study highlights the indispensable role of TIRAP-PKCδ in p38 MAPK-activation, NF-κB- and AP-1-mediated proinflammatory cytokines expression, whereas DZD significantly attenuated the signaling. Conclusion: Targeting TIRAP-PKCδ interaction by DZD is a novel therapeutic approach for treating sepsis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AP1 | |
| 650 | 4 | |a NF-κB | |
| 650 | 4 | |a PKCδ | |
| 650 | 4 | |a TIRAP | |
| 650 | 4 | |a dorzolamide (DZD) | |
| 650 | 4 | |a macrophages | |
| 650 | 4 | |a p38 MAPK | |
| 650 | 4 | |a pro-inflammatory cytokines | |
| 650 | 4 | |a sepsis | |
| 700 | 1 | |a Kumar, Ashutosh |e verfasserin |4 aut | |
| 700 | 1 | |a Gaponenko, Vadim |e verfasserin |4 aut | |
| 700 | 1 | |a Thurston, Teresa Lm |e verfasserin |4 aut | |
| 700 | 1 | |a Mehta, Dolly |e verfasserin |4 aut | |
| 700 | 1 | |a Faisal, Syed M |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Kam Yj |e verfasserin |4 aut | |
| 700 | 1 | |a Jha, Hem C |e verfasserin |4 aut | |
| 700 | 1 | |a Darwhekar, Gajanan N |e verfasserin |4 aut | |
| 700 | 1 | |a Baig, Mirza S |e verfasserin |4 aut | |
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