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Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50–Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome
- Source :
- The Journal of Immunology. 199:2043-2054
- Publication Year :
- 2017
- Publisher :
- The American Association of Immunologists, 2017.
-
Abstract
- Acute respiratory distress syndrome (ARDS) is a severe illness characterized by uncontrolled inflammation. The resolution of inflammation is a tightly regulated event controlled by endogenous mediators, such as resolvin D1 (RvD1). Cyclooxygenase-2 (COX-2) has been reported to promote inflammation, along with PGE2, in the initiation of inflammation, as well as in prompting resolution, with PGD2 acting in the later phase of inflammation. Our previous work demonstrated that RvD1 enhanced COX-2 and PGD2 expression to resolve inflammation. In this study, we investigated mechanisms underlying the effect of RvD1 in modulating proresolving COX-2 expression. In a self-limited ARDS model, an LPS challenge induced the biphasic activation of COX-2, and RvD1 promoted COX-2 expression during the resolution phase. However, it was significantly blocked by treatment of a NF-κB inhibitor. In pulmonary fibroblasts, NF-κB p50/p50 was shown to be responsible for the proresolving activity of COX-2. Additionally, RvD1 potently promoted p50 homodimer nuclear translocation and robustly triggered DNA-binding activity, upregulating COX-2 expression via lipoxin A4 receptor/formyl peptide receptor 2. Finally, the absence of p50 in knockout mice prevented RvD1 from promoting COX-2 and PGD2 expression and resulted in excessive pulmonary inflammation. In conclusion, RvD1 expedites the resolution of inflammation through activation of lipoxin A4 receptor/formyl peptide receptor 2 receptor and NF-κB p50/p50–COX-2 signaling pathways, indicating that RvD1 might have therapeutic potential in the management of ARDS.
- Subjects :
- 0301 basic medicine
ARDS
Infectious Disease and Host Response
P50
biology
business.industry
Immunology
Inflammation
medicine.disease
Formyl peptide receptor 2
03 medical and health sciences
030104 developmental biology
Knockout mouse
medicine
Cancer research
biology.protein
Immunology and Allergy
Cyclooxygenase
medicine.symptom
Signal transduction
business
Receptor
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 199
- Database :
- OpenAIRE
- Journal :
- The Journal of Immunology
- Accession number :
- edsair.doi.dedup.....fa3eca941ed5098b069a279468a2f006