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- W4313354664 abstract "Abstract Since anti-inflammatory activity of prostaglandin D2 (PGD2) is attributed to 15-deoxy-Δ12,14-PGJ2, a byproduct of PGD2, we explored the hypothesis that PGD2, independent of 15-deoxy-Δ12,14-PGJ2, activates NF-E2-related factor 2 (Nrf2), an anti-inflammatory transcription factor, contributing to suppression of lung inflammation in acute lung injury (ALI). Intratracheal delivery of PGD2 decreased neutrophilic infiltration, MPO activity, and the production of pro-inflammatory cytokines in LPS-treated lungs. In contrast, lipocalin-prostaglandin D synthase (L-PGDS) KO mice that produce less PGD2 showed prolonged lung inflammation, highlighting the importance of L-PGDS and PGD2 in suppressing lung inflammation. Two log10 less of PGD2 than 15-deoxy-Δ12,14-PGJ2 was sufficient for activating Nrf2 in RAW 264.7. Similarly, PGD2 was more potent than 15-deoxy-Δ12,14-PGJ2 in expressing Nrf2 dependent genes in mouse lungs. While overexpression of DP1, a receptor of PGD2, enhanced PGD2-mediated Nrf2 activation, siRNA silencing DP1 expression reduced its activation, suggesting that PGD2 uses DP1 in activating Nrf2. Furthermore, PGD2 synergistically suppressed neutrophil infiltration when nrf2 was functionally complemented to the lung of the nrf2-/- mice. Our results show that PGD2 activated Nrf2 independent of 15-deoxy-Δ12,14-PGJ2 and involved DP1. We suggest that PGD2 has a potent anti-inflammatory activity, which is at least in part mediated by activating Nrf2." @default.
- W4313354664 created "2023-01-06" @default.
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- W4313354664 date "2013-05-01" @default.
- W4313354664 modified "2023-10-05" @default.
- W4313354664 title "Prostaglandin D2 ameliorates acute lung inflammation by activating Nrf2 independent of 15-deoxy-Δ12,14-PGJ2. (P5040)" @default.
- W4313354664 doi "https://doi.org/10.4049/jimmunol.190.supp.180.3" @default.
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