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Increased expression levels of inflammatory cytokines and adhesion molecules in lipopolysaccharide?induced acute inflammatory apoM?/? mice.

ABSTRACT: Apolipoprotein M (apoM) may serve a protective role in the development of inflammation. Nuclear factor??B (NF??B) and its downstream factors (including a number of inflammatory cytokines and adhesion molecules) are essential for the regulation of inflammatory processes. In the present study, the importance of apoM in lipopolysaccharide (LPS)?induced acute inflammation and its potential underlying mechanisms, were investigated using an apoM?knockout mouse model. The levels of inducible nitric oxide synthase (iNOS), NF??B, interleukin (IL)?1?, intercellular adhesion molecule 1 (ICAM?1) and vascular cell adhesion protein 1 (VCAM?1) were detected using reverse transcription?quantitative PCR and western blotting. The serum levels of IL?6 and IL?10 were detected using Luminex technology. The results demonstrated that the protein levels of iNOS, NF??B, IL?1?, ICAM?1 and VCAM?1 were significantly increased in apoM?/? mice compared with those in apoM+/+ mice. In addition, two?way ANOVA revealed that the interaction between apoM and LPS had a statistically significant effect on a number of factors, including the mRNA expression levels of hepatic iNOS, NF??B, IL?1?, ICAM?1 and VCAM?1. Notably, the effects of apoM and 10 mg/kg LPS on the levels of IL?6 and IL?10 were the opposite of those induced by 5 mg/kg LPS, which could be associated with the dual anti? and pro?inflammatory effects of IL?6 and IL?10. Collectively, the results of the present study revealed that apoM is an important regulator of inflammatory cytokine and adhesion molecule production in LPS?induced inflammation, which may consequently be associated with the severity of inflammation. These findings indicated that the anti?inflammatory effects of apoM may partly result from the inhibition of the NF??B pathway.

SUBMITTER: Shi Y

PROVIDER: S-EPMC7453663 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Increased expression levels of inflammatory cytokines and adhesion molecules in lipopolysaccharide‑induced acute inflammatory apoM‑/‑ mice.

Shi Yuanping Y Liu Hongyao H Liu Hong H Yu Yang Y Zhang Jun J Li Yanfei Y Luo Guanghua G Zhang Xiaoying X Xu Ning N

Molecular medicine reports 20200811 4

Apolipoprotein M (apoM) may serve a protective role in the development of inflammation. Nuclear factor‑κB (NF‑κB) and its downstream factors (including a number of inflammatory cytokines and adhesion molecules) are essential for the regulation of inflammatory processes. In the present study, the importance of apoM in lipopolysaccharide (LPS)‑induced acute inflammation and its potential underlying mechanisms, were investigated using an apoM‑knockout mouse model. The levels of inducible nitric oxi ...[more]

PMID: 32945469

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Project description:Menopause, the cessation of menses, occurs with estrogens decline, low-grade inflammation, and impaired endothelial function, contributing to atherosclerotic risk. Intima-media thickness (IMT) is an early subclinical biomarker of atherosclerosis. Inflammation may have a role on symptoms: hot flashes, anxiety, and depressive mood, which also are related to endothelial dysfunction, increased IMT and cardiovascular risk. In this study we compared several inflammatory markers in early vs. late postmenopausal women and studied the association of IMT and symptoms with these markers in the full sample. In a cross-sectional design including 60 women (53.1 ± 4.4 years old) at early and late postmenopause, we evaluated the expression of CD62L, ICAM-1, PSGL-1, CD11b, CD11c, and IL-8R on PBMC by flow cytometry. Serum soluble ICAM-1, sVCAM-1, sCD62E, sCD62P, CXCL8, IL-1β, IL-6, and TNF-α levels were quantified by ELISA. Plasma levels of microparticles (MPs) were determined by FACS. Finally, carotid intima-media thickness (IMT) was measured by ultrasound. We observed that ICAM-1 expression by lymphocytes and serum sVCAM-1 levels were augmented at late postmenopause. Late postmenopause women with severe hot flashes had increased expression of CD62L and IL-8R on neutrophils. By multivariate analysis, the carotid IMT was strongly associated with membrane-bound TNF-α, CD11b expression, Annexin V(+) CD3(+) MPs, LPS-induced NO production, HDL-cholesterol and age. Depressive mood was associated negatively with PSGL-1 and positively with LPS-induced NO. Finally, Log(AMH) levels were associated with carotid IMT, IL-8R expression and time since menopause. IMT and depressive mood were the main clinical features related to vascular inflammation. Aging, hormonal changes and obesity were also related to endothelial dysfunction. These findings provide further evidence for a link between estrogen deficiency and low-grade inflammation in endothelial impairment in mature women.

Dataset Information

Increased expression levels of inflammatory cytokines and adhesion molecules in lipopolysaccharide?induced acute inflammatory apoM?/? mice.

Publications

Increased expression levels of inflammatory cytokines and adhesion molecules in lipopolysaccharide‑induced acute inflammatory apoM‑/‑ mice.

Similar Datasets

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