S-Alk(en)ylmercaptocysteine suppresses LPS-induced pro-inflammatory responses in murine macrophages through inhibition of NF-κB pathway and modulation of thiol redox status
Published by Elsevier Inc..
The Allium vegetable-derived metabolite, S-alk(en)ylmercaptocysteine (CySSR), has been reported to modulate oxidative stress and inflammatory responses. However, the underlying mechanisms of action and structure-activity relationships are not completely understood. We investigated the mechanistic basis of the protective effects of CySSR on pro-inflammatory responses involving redox/oxidative stress induced by E. coli lipopolysaccharide (LPS) using RAW 264.7 cells. CySSR (R = allyl, "A" or 1-propenyl, "Pe") pre-treatments conferred concentration-dependent reductions in cytokines (TNF-α, IL-1β and IL-6), NO production and iNOS (inducible nitric synthase) overexpression, and attenuated oxidant production in LPS-stimulated RAW 264.7 cells where viability remained > 90%. These protective effects were manifested through inhibited activation of the nuclear factor-kappa B (NF-κB) signaling pathway via suppression of the IκB kinases (IKK) phosphorylation possibly by transforming growth factor β-activated kinase 1 or a kinase further upstream the canonical NF-κB signaling pathway. The attenuation of LPS-induced inflammation by CySSRs was associated with enhanced levels of cellular cysteine (CySH) and glutathione (GSH) mediated by cellular import/reduction of CySSR and the induction of glutamate cysteine ligase (GCL), one of > 200 nuclear factor erythroid 2-related factor 2 (Nrf2) regulated proteins. The reduction of anti-inflammatory effect of CySSR following pretreatment of cells with L-buthionine-S,R-sulfoximine (BSO) implicates GSH having a major role in reducing inflammation, likely in the context of other Nrf2-regulated antioxidant enzymes that scavenge H2O2 and peroxides using GSH as co-substrate. The anti-inflammatory effect of CySSPe was significantly greater than CySSA for almost all indicators measured, and cell metabolites of CySSRs may have a role in attenuating NF-κB signaling.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2018 |
|---|---|
| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:129 |
|---|---|
| Enthalten in: |
Free radical biology & medicine - 129(2018) vom: 15. Dez., Seite 548-558 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Tocmo, Restituto [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 27.09.2019 Date Revised 27.09.2019 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.freeradbiomed.2018.10.424 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM289766249 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM289766249 | ||
| 003 | DE-627 | ||
| 005 | 20231225063254.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2018 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.freeradbiomed.2018.10.424 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0965.xml |
| 035 | |a (DE-627)NLM289766249 | ||
| 035 | |a (NLM)30342185 | ||
| 035 | |a (PII)S0891-5849(18)31480-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Tocmo, Restituto |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a S-Alk(en)ylmercaptocysteine suppresses LPS-induced pro-inflammatory responses in murine macrophages through inhibition of NF-κB pathway and modulation of thiol redox status |
| 264 | 1 | |c 2018 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 27.09.2019 | ||
| 500 | |a Date Revised 27.09.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Published by Elsevier Inc. | ||
| 520 | |a The Allium vegetable-derived metabolite, S-alk(en)ylmercaptocysteine (CySSR), has been reported to modulate oxidative stress and inflammatory responses. However, the underlying mechanisms of action and structure-activity relationships are not completely understood. We investigated the mechanistic basis of the protective effects of CySSR on pro-inflammatory responses involving redox/oxidative stress induced by E. coli lipopolysaccharide (LPS) using RAW 264.7 cells. CySSR (R = allyl, "A" or 1-propenyl, "Pe") pre-treatments conferred concentration-dependent reductions in cytokines (TNF-α, IL-1β and IL-6), NO production and iNOS (inducible nitric synthase) overexpression, and attenuated oxidant production in LPS-stimulated RAW 264.7 cells where viability remained > 90%. These protective effects were manifested through inhibited activation of the nuclear factor-kappa B (NF-κB) signaling pathway via suppression of the IκB kinases (IKK) phosphorylation possibly by transforming growth factor β-activated kinase 1 or a kinase further upstream the canonical NF-κB signaling pathway. The attenuation of LPS-induced inflammation by CySSRs was associated with enhanced levels of cellular cysteine (CySH) and glutathione (GSH) mediated by cellular import/reduction of CySSR and the induction of glutamate cysteine ligase (GCL), one of > 200 nuclear factor erythroid 2-related factor 2 (Nrf2) regulated proteins. The reduction of anti-inflammatory effect of CySSR following pretreatment of cells with L-buthionine-S,R-sulfoximine (BSO) implicates GSH having a major role in reducing inflammation, likely in the context of other Nrf2-regulated antioxidant enzymes that scavenge H2O2 and peroxides using GSH as co-substrate. The anti-inflammatory effect of CySSPe was significantly greater than CySSA for almost all indicators measured, and cell metabolites of CySSRs may have a role in attenuating NF-κB signaling | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Lipopolysaccharide | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a S-alk(en)ylmercaptocysteine | |
| 650 | 4 | |a Thiol redox status | |
| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a IL1B protein, mouse |2 NLM | |
| 650 | 7 | |a Interleukin-1beta |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a NF-E2-Related Factor 2 |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a Nfe2l2 protein, mouse |2 NLM | |
| 650 | 7 | |a S-allylmercaptocysteine |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a interleukin-6, mouse |2 NLM | |
| 650 | 7 | |a S-propylmercaptocysteine |2 NLM | |
| 650 | 7 | |a 2280-26-4 |2 NLM | |
| 650 | 7 | |a Buthionine Sulfoximine |2 NLM | |
| 650 | 7 | |a 5072-26-4 |2 NLM | |
| 650 | 7 | |a Nitric Oxide Synthase Type II |2 NLM | |
| 650 | 7 | |a EC 1.14.13.39 |2 NLM | |
| 650 | 7 | |a Nos2 protein, mouse |2 NLM | |
| 650 | 7 | |a EC 1.14.13.39 |2 NLM | |
| 650 | 7 | |a I-kappa B Kinase |2 NLM | |
| 650 | 7 | |a EC 2.7.11.10 |2 NLM | |
| 650 | 7 | |a Glutamate-Cysteine Ligase |2 NLM | |
| 650 | 7 | |a EC 6.3.2.2 |2 NLM | |
| 650 | 7 | |a Glutathione |2 NLM | |
| 650 | 7 | |a GAN16C9B8O |2 NLM | |
| 650 | 7 | |a Cysteine |2 NLM | |
| 650 | 7 | |a K848JZ4886 |2 NLM | |
| 700 | 1 | |a Parkin, Kirk |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Free radical biology & medicine |d 1989 |g 129(2018) vom: 15. Dez., Seite 548-558 |w (DE-627)NLM012613827 |x 1873-4596 |7 nnns |
| 773 | 1 | 8 | |g volume:129 |g year:2018 |g day:15 |g month:12 |g pages:548-558 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.freeradbiomed.2018.10.424 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 129 |j 2018 |b 15 |c 12 |h 548-558 | ||