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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Sulforaphane suppressed LPS-induced inflammation in mouse peritoneal macrophages through Nrf2 dependent pathway
Wen Lin1, Rachel T Wu, Tienyuan Wu
1Graduate Program in Pharmaceutical Science, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Abstract:
Sulforaphane (SFN) is a natural isothiocyanate that is present in cruciferous vegetables such as broccoli and cabbage. Previous studies have shown that SFN is effective in preventing carcinogenesis induced by carcinogens in rodents, which is related in part to its potent anti-inflammation properties. In the present study, we compared the anti-inflammatory effect of SFN on LPS-stimulated inflammation in primary peritoneal macrophages derived from Nrf2 (+/+) and Nrf2 (-/-) mice. Pretreatment of SFN in Nrf2 (+/+) primary peritoneal macrophages potently inhibited LPS-stimulated mRNA expression, protein expression and production of TNF-alpha, IL-1beta, COX-2 and iNOS. HO-1 expression was significantly augmented in LPS-stimulated Nrf2 (+/+) primary peritoneal macrophages by SFN. Interestingly, the anti-inflammatory effect was attenuated in Nrf2 (-/-) primary peritoneal macrophages. We concluded that SFN exerts its anti-inflammatory activity mainly via activation of Nrf2 in mouse peritoneal macrophages.
Insights
Sulforaphane (SFN), a compound in cruciferous vegetables, shows anti-inflammatory effects by activating Nrf2. This pathway is crucial for SFN
Area of Science:
- Biochemistry
- Immunology
- Molecular Biology
Background:
- Sulforaphane (SFN) is a natural isothiocyanate found in cruciferous vegetables.
- SFN has demonstrated anti-carcinogenic properties, partly due to its anti-inflammatory effects.
Purpose of the Study:
- To investigate the anti-inflammatory effects of SFN on lipopolysaccharide (LPS)-stimulated macrophages.
- To compare the efficacy of SFN in Nrf2 (nuclear factor erythroid 2-related factor 2) wild-type and knockout mouse models.
Main Methods:
- Primary peritoneal macrophages were isolated from Nrf2 (+/+) and Nrf2 (-/-) mice.
- Macrophages were pretreated with SFN and subsequently stimulated with LPS.
- mRNA and protein expression of inflammatory markers (TNF-alpha, IL-1beta, COX-2, iNOS) and HO-1 were analyzed.
Main Results:
- SFN significantly inhibited LPS-induced mRNA and protein expression of TNF-alpha, IL-1beta, COX-2, and iNOS in Nrf2 (+/+) macrophages.
- SFN markedly increased HO-1 expression in LPS-stimulated Nrf2 (+/+) macrophages.
- The anti-inflammatory effects of SFN were attenuated in Nrf2 (-/-) macrophages.
Conclusions:
- Sulforaphane exerts its primary anti-inflammatory activity through the activation of the Nrf2 pathway in mouse peritoneal macrophages.
- Nrf2 is a key mediator of SFN's protective effects against inflammation.