Coordinated action of microsomal prostaglandin E synthase-1 and prostacyclin synthase on contact hypersensitivity.
Biochem Biophys Res Commun
; 546: 124-129, 2021 03 26.
Article
en En
| MEDLINE
| ID: mdl-33582554
ABSTRACT
Microsomal prostaglandin (PG) E synthase-1 (mPGES-1) and prostacyclin (PGI2) synthase (PGIS) are PG terminal synthases that work downstream of cyclooxygenase and synthesize PGE2 and PGI2, respectively. Although the involvement of PG receptors in acquired cutaneous immune responses was recently shown, the roles of these PG terminal synthases remain unclear. To identify the pathophysiological roles of mPGES-1 and PGIS in cutaneous immune systems, we applied contact hypersensitivity (CHS) to mPGES-1 and PGIS knockout (KO) mice as a model of acquired immune responses. Mice were treated with 1-fluoro-2,4-dinitrobenzene (DNFB) and evaluated for ear thickness and histopathological features. The results showed that the severity of ear swelling in both gene-deficient mice was much lower than that in wild-type (WT) mice. Histological examination of DNFB-treated ears showed that inflammatory cell infiltration and edema in the dermis were also less apparent in both genotypic mice. LC-MS analysis further showed that the increment in PGE2 levels in DNFB-treated ear tissue was reduced in mPGES-1 KO mice, and that 6-keto PGF1α (a stable metabolite of PGI2) was not detected in PGIS KO mice. Furthermore, we made bone marrow (BM) chimera and found that transplantation of WT mouse-derived BM cells restored the impaired CHS response in mPGES-1 KO mice but did not restore the response in PGIS KO mice. These results indicated that mPGES-1 in BM-derived cells and PGIS in non-BM-derived cells might play critical roles in DNFB-induced CHS. mPGES-1-derived PGE2 and PGIS-derived PGI2 might coordinately promote acquired cutaneous immune responses.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oxidorreductasas Intramoleculares
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Sistema Enzimático del Citocromo P-450
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Dermatitis por Contacto
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Prostaglandina-E Sintasas
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article