Interleukin-1β and interleukin-6 increase levels of apolipoprotein B mRNA and decrease accumulation of its protein in culture medium of HepG2 cells

Abstract

The purpose of the present study was to examine the regulation of levels of apolipoprotein B (apoB) mRNA and its protein by cytokines in HepG2 cells. A dose-dependent increase in apoB mRNA levels was observed in the presence of either interleukin-1 ␤ (IL-1 ␤ ) or IL-6 alone. This increase occurred as early as 1 h after IL-1 ␤ or IL-6 stimulation. Exogenous addition of IL-1 ␤ (5 ng/ml) and IL-6 (50 ng/ml) induced 2.8-and 2.1-fold increases as a result of 18 h of culture, respectively. Co-stimulation with IL-1 ␤ and IL-6 significantly enhanced the increase in apoB mRNA levels stimulated with either cytokine alone. Treatment with cycloheximide prevented the induction of apoB mRNA by IL-1 ␤ , but not by IL-6. These findings suggest that enhancement of apoB mRNA levels by these cytokines is mediated through different pathways. Conversely, IL-1 ␤ and IL-6 lowered the accumulation of apoB protein levels in the culture medium. The pulse-chase study showed that addition of N-acetyl leucyl leucyl norleucinal to the medium induced a decrease in newly synthesized apoB in the cell lysate in response to IL-1 ␤ ( P Ͻ 0.05) or IL-6 (not to a significant extent) compared with control. These findings demonstrated that the lower level of apoB in the medium was caused by the enhanced intracellular degradation. In addition, IL-1 ␤ increased LDL receptor mRNA levels as well as protein activity, although IL-6 did not, suggesting that the more marked decrease in apoB accumulation in the medium induced by IL-1 ␤ compared with that induced by IL-6 may reflect an increased uptake of apoB from the medium by IL-1 ␤ . The present study demonstrates that a cytokine network may be involved in the metabolism of apoB under certain conditions such as inflammation.-Yokoyama, K., T. Ishibashi, L. Yiqiang, A. Nagayoshi, T. Teramoto, and Y. Maruyama. Interleukin-1 ␤ and interleukin-6 increase levels of apolipoprotein B mRNA and decrease accumulation of its protein in culture medium of HepG2 cells.

α‐Lipoic acid up‐regulates gene expression but reduces protein levels of fibroblast growth factor 21 in HepG2 cells

“…Protein synthesis is a process that is regulated by gene transcription, protein translation and posttranslational processing, of which there is deviation under some conditions 51–53 . This study further supports the deviation of gene transcription and protein synthesis under certain conditions.…”

“…Protein synthesis is a process that is regulated by gene transcription, protein translation and posttranslational processing, of which there is deviation under some conditions. [51][52][53] This study further supports the deviation of gene transcription and protein synthesis under certain conditions. A few reports showed the stimulatory effects of ALA on FGF21 gene expression and protein synthesis in both HepG2 cells and primary culture hepatocytes.…”

Serum Protein Profiling of Adults and Children With Crohn Disease

“…Even if several studies support the concept that APOB levels were significantly lower in patients CD than in healthy controls (38,39), when we compared CD paediatric and adult populations we observed higher protein levels of APOB in sera from children, indicating that serum APOB may be a primary predictor of inflammatory markers in early‐onset disease (40). It is known that the production of APOB is affected by transcription, messenger RNA stability, translation, posttranslational processing, secretion, and reuptake (40). Recently, Song and Gray (41) reported that APOB levels were significantly higher among early‐onset subjects with type 2 diabetes mellitus compared with those with a later‐onset disease.…”

“…Most of the proteins identified in the present study were similarly expressed among children and adults; however, CERU and APOB were found to be upregulated in the children patients with CD compared with adult-onset, whereas CLUS was found to be upregulated in the adult patients with CD. Even if several studies support the concept that APOB levels were significantly lower in patients CD than in healthy controls (38,39), when we compared CD paediatric and adult populations we observed higher protein levels of APOB in sera from children, indicating that serum APOB may be a primary predictor of inflammatory markers in early-onset disease (40). It is known that the production of APOB is affected by transcription, messenger RNA stability, translation, posttranslational processing, secretion, and reuptake (40).…”

Biphasic adaptative responses in VLDL metabolism and lipoprotein homeostasis during Gram-negative endotoxemia

“…However, numerous studies have shown changes in hepatic apoB mRNA levels under a variety of inflammatory conditions. 18,19 In rats, we found that apoB mRNA levels increased in periportal and perivenous hepatocytes in response to LPS injection 14,20 and that exposure of primary hepatocytes to LPS-stimulated Kupffer cell-conditioned medium 15 or to individual or combined pro-inflammatory cytokines led to augmented apoB mRNA expression. 15,21,22 We hypothesized that, during the APR, transcriptional or post-transcriptional regulation affecting apoB mRNA levels might occur supplying more apoB competent for VLDL assembly, given that apoB secretion was enhanced in all cases.…”