Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0036690 (
sepsis
)
59,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sepsis
is a systemic inflammation accompanied by multi-organ dysfunction due to microbial infection. Prostaglandins and their metabolites have long been studied for their importance in regulating the innate immune response. 15-keto-PGE2 (15k-PGE
2
) is a prostaglandin E2 (PGE
2
) metabolite, whose further processing is catalyzed by
prostaglandin reductase 2
(
PTGR2
). We showed disruption of the Ptgr2 gene in mice improves the survival rate under both LPS- and cecum ligation/puncture (CLP)-induced experimental
sepsis
. Knockdown of
PTGR2
showed significant accumulation of intracellular 15k-PGE
2
in activated macrophages. Both
PTGR2
knockdown and exogenous treatment with 15k-PGE
2
resulted in reduced pro-inflammatory cytokines production in LPS-stimulated RAW264.7 cells or bone marrow-derived macrophages (BMDM). The same treatment in RAW264.7 and BMDM also led to increased levels of the anti-oxidative transcription factor, Nuclear factor (erythroid-2) related factor-2 (NRF2), augmented anti-oxidant response element (ARE)-mediated reporter activity and upregulated expression of the corresponding anti-oxidant genes. 15k-PGE
2
further demonstrated modification to Kelch-like ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, at cysteine 288 (Cys288) site post-translationally. Finally, 15k-PGE
2
-treated mice were found to be more resistant to experimental
sepsis
. Taken together, our study affirms the significance of
PTGR2
and 15k-PGE
2
in mitigating inflammatory responses and suggests a novel anti-oxidative and anti-inflammatory therapy for
sepsis
through targeting
PTGR2
and administering15k-PGE
2
.
...
PMID:Targeting the 15-keto-PGE2-PTGR2 axis modulates systemic inflammation and survival in experimental sepsis. 2917 86
