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-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 oxide synthase (iNOS), NF-κB, interleukin (IL)-1β, 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-κB, IL-1β, 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-κB, IL-1β, 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-κB pathway.

Adipose-Derived Lipid-Binding Proteins: The Good, the Bad and the Metabolic Diseases

“…Goto-Kakizaki rats, a non-obese, spontaneous model of diabetic rats display better insulin sensitivity when overexpressing Apom, concomitantly with an increased insulin secretion and glucose utilization [106]. Concordant results were obtained in Apom-deficient mice which present impaired insulin sensitivity, high plasma inflammatory markers such as IL-6 or IL-1β, and hepatic NF-κB [99,107]. Yao et al also recently demonstrated that APOM is expressed in murine and human macrophages, interacts with the scavenger receptor BI to promote cholesterol efflux from the phagocytic cells and protects against atherosclerosis [108,109].…”

Propofol promotes migration, alleviates inflammation, and apoptosis of lipopolysaccharide‐induced human pulmonary microvascular endothelial cells by activating PI3K/AKT signaling pathway via upregulating APOM expression

“…For instances, APOM could repress oxidized low‐density lipoprotein (ox‐LDL) ‐induced inflammation, thereby protecting the vascular endothelium (Zheng et al, 2019). It has been demonstrated that the levels of inflammatory cytokines are elevated in LPS‐induced APOM‐knockout mouse model (Shi et al, 2020). Besides, compelling evidence indicate that APOM deletion induces apoptosis in mouse kidney (Pei et al, 2018).…”

Non-Excitatory Amino Acids, Melatonin, and Free Radicals: Examining the Role in Stroke and Aging

“…NO is a small molecule synthesized by NOS named neuronal NOS (nNOS) and endothelial (eNOS), which are constitutive isoforms, and the iNOS that is negligible in resting cells but is induced by inflammatory cytokines and LPS [358,359,362,367,368]. LPS binds to the TLR4 on the surface of macrophage membranes, leading to the activation of MAPK or NF-κB signaling pathways and further iNOS gene expression [369] to produce NO. Additionally, microglia can exhibit a pro-inflammatory phenotype by LPS contributing to the activation of iNOS.…”