Microsomal prostaglandin (PG) E(2) synthase-1 (mPGES-1) catalyzes the terminal step in the biosynthesis of PGE(2), a key proinflammatory mediator. The purpose of this study was to elucidate the regulation of mPGES-1 mRNA expression in cardiomyocytes, define the role of JNK enzymes in this process, and characterize the role of mPGES-1 in cardiomyocyte PGE(2) biosynthesis. In neonatal cardiomyocytes, interleukin-1beta and lipopolysaccharide (LPS) both stimulated mPGES-1 mRNA expression and increased mPGES-1 mRNA stability and protein synthesis but failed to increase mPGES-1 mRNA transcription. Treatment with the JNK1/2 inhibitor, SP600125, abrogated the increases in mPGES-1 mRNA stability, mPGES-1 protein synthesis, and PGE(2) release induced by interleukin-1beta or LPS. mPGES-1 protein synthesis was observed in LPS-stimulated neonatal cardiomyocytes from jnk1(-/-) or jnk2(-/-) mice. In contrast, infection of jnk1(-/-) cardiomyocytes with an adenovirus encoding phosphorylation-resistant JNK2 (ad-JNK2-DN), or of jnk2(-/-) cardiomyocytes with ad-JNK1-DN, significantly decreased LPS-stimulated mPGES-1 protein synthesis. Similarly, co-infection with ad-JNK1-DN and ad-JNK2-DN attenuated LPS-stimulated mPGES-1 protein synthesis in cardiomyocytes from wild type mice. Targeted deletion of the gene encoding mPGES-1 led to a 3.2-fold decrease in LPS-stimulated PGE(2) release by cardiomyocytes in comparison with wild type cells but had no effect on COX-1, COX-2, mPGES-2, or cytosolic PGES mRNA levels. These studies provide direct evidence that mPGES-1 mRNA levels in cardiomyocytes are augmented by stabilization of mPGES-1 mRNA, that JNK1 or JNK2 can participate in the regulation of mPGES-1 protein synthesis in these cells, and that mPGES-1 catalyzes the majority of LPS-induced PGE(2) biosynthesis by cardiomyocytes.
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http://dx.doi.org/10.1074/jbc.M602815200 | DOI Listing |
Int J Mol Sci
November 2024
Department of Regulation Biochemistry, Kitasato University Graduate School of Medical Sciences, Sagamihara 252-0373, Japan.
Microsomal prostaglandin E synthase-1 (mPGES-1) is an isozyme of the prostaglandin (PG) E synthase that acts downstream of cyclooxygenase and catalyzes the conversion of PGH to PGE. The impact of genetic deletion of mPGES-1 on the development of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis, a well-established model of inflammatory bowel disease (IBD), was investigated in this study. After administration of TNBS, mice deficient in mPGES-1 (mPGES-1 mice) showed more severe colitis than did wild-type (WT) mice.
View Article and Find Full Text PDFFront Vet Sci
May 2024
Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China.
Aims: The aim of this study was to investigate the effects of aspirin eugenol ester (AEE) on ileal immune function in broilers under lipopolysaccharide (LPS)-induced immune stress.
Methods: Two hundred and forty one-day-old male Arbor Acres chicks were randomly divided into four groups (saline, LPS, saline + AEE and LPS + AEE) with six replicates of ten broilers each. The saline group and LPS group were fed the normal diet, while the other two groups received normal diet plus 0.
Poult Sci
July 2024
Department of Animal Physiology, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471003, China; Innovative Research Team of Livestock Intelligent Breeding and Equipment, Longmen Laboratory, Luoyang 471023, China; Henan International Joint Laboratory of Animal Welfare and Health Breeding, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471023, China. Electronic address:
This study was designed to examine the impact of aspirin eugenol ester (AEE) on the growth performance, serum antioxidant capacity, jejunal barrier function, and cecal microbiota of broilers raised under stressful high density (HD) stocking conditions compared with normal density broilers (ND). A total of 432 one-day-old AA+ male broilers were randomly divided into 4 groups: normal density (ND, 14 broilers /m), high density (HD, 22 broilers /m), ND + AEE, and HD + AEE. The results of the study revealed a significant decrease in the growth performance of broiler chickens as a result of HD stress (P < 0.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2023
Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, State Key Laboratory of Dampness Syndrome of Chinese Medicine, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou, Guangdong Province, PR China. Electronic address:
Ethnopharmacological Relevance: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used clinically to treat inflammatory diseases clinically. However, the adverse effects of NSAIDs cannot be ignored. Therefore, it is critical for us to find alternative anti-inflammatory drugs that can reduce adverse reactions to herbal medicine, such as Iris tectorum Maxim.
View Article and Find Full Text PDFNat Commun
January 2023
Department of Cardiothoracic Surgery, Weill Cornell Medicine, 525 East 68th street, New York, NY, 10065, USA.
IRE1α-XBP1 signaling is emerging as a central orchestrator of malignant progression and immunosuppression in various cancer types. Employing a computational XBP1s detection method applied to TCGA datasets, we demonstrate that expression of the XBP1s mRNA isoform predicts poor survival in non-small cell lung cancer (NSCLC) patients. Ablation of IRE1α in malignant cells delays tumor progression and extends survival in mouse models of NSCLC.
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