Interleukin-6 down-regulates expressions of the aldolase B and albumin genes through a pathway involving the activation of tyrosine kinase

Huang, Yong; Shinzawa, Haruhide; Togashi, Hitoshi; Takahashi, Tsuneo; Kuzumaki, Takejiro; Otsu, Kaoru; Ishikawa, Kiichi

doi:10.1016/0003-9861(95)90001-2

Cited by 35 publications

(23 citation statements)

References 36 publications

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“…Interestingly, it has been demonstrated that IL-6 is able to reduce albumin mRNA expressions [19]. On the other hand, it is known that CSU is associated with increased circulating concentration of IL-6 [5].…”

Section: Discussionmentioning

confidence: 99%

Chronic Spontaneous Urticaria Is Characterized by Lower Serum Advanced Glycation End-Products

Grzanka

Damasiewicz-Bodzek

Machura

et al. 2014

BioMed Research International

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Background. Chronic spontaneous urticaria (CSU) is associated with activation of acute phase response. On the other hand, it is known that systemic inflammation may lead to increased formation of advanced glycation end-products (AGEs), associated with pathogenesis of various diseases. Aim. We aim to test whether chronic inflammation manifested by activated acute phase response may provide a mechanism for increased serum AGEs concentration in CSU. Methods. Concentrations of AGEs were measured spectrofluorimetrically in serum of CSU patients and the healthy subjects. Results. Serum AGEs and albumin concentrations in CSU patients were significantly lower as compared with the healthy subjects. Serum CRP concentration was significantly higher in patients with CSU than in the controls. Significant positive correlation was observed between AGEs and albumin concentrations in the subjects. Conclusions. CSU is not associated with increased circulating AGEs concentrations, despite the enhanced systemic inflammatory response. Paradoxical decrease of serum AGEs concentrations is probably a reflection of lower concentration of “negative acute phase proteins” such as albumin.

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Section: Discussionmentioning

confidence: 99%

Chronic Spontaneous Urticaria Is Characterized by Lower Serum Advanced Glycation End-Products

Grzanka

Damasiewicz-Bodzek

Machura

et al. 2014

BioMed Research International

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“…Total RNA was isolated using TRIzol (Life Technologies) as described by the manufacturer's protocol. Northern blot analysis was conducted as previously described (26). Briefly, the isolated RNA was separated by agarose gel electrophoresis, transferred to a Nytran membrane, and probed for mRNA using a 32 P-labeled murine Bf cDNA probe, and radioactive bands were developed by autoradiography.…”

Section: Isolation Of Total Cellular Rna and Northern Blot Analysismentioning

confidence: 99%

Complement Factor B Gene Regulation: Synergistic Effects of TNF-α and IFN-γ in Macrophages

Huang

Krein

Muruve

et al. 2002

The Journal of Immunology

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Complement factor B (Bf) plays an important role in activating the alternative complement pathway. The inflammatory cytokines, in particular TNF-α and IFN-γ, are critical in the regulation of Bf gene expression in macrophages. In this study, we investigated the mechanisms of Bf gene regulation by TNF-α and IFN-γ in murine macrophages. Northern analysis revealed that Bf mRNA expression was synergistically up-regulated by TNF-α and IFN-γ in MH-S cells. Truncations of the 5′ Bf promoter identified a region between −556 and −282 bp that mediated TNF-α responsiveness as well as the synergistic effect of TNF-α and IFN-γ on Bf expression. Site-directed mutagenesis of a NF-κB-binding element in this region (−433 to −423 bp) abrogated TNF-α responsiveness and decreased the synergistic effect of TNF-α and IFN-γ on Bf expression. EMSAs revealed nuclear protein binding to this NF-κB cis-binding element on TNF-α stimulation. Supershift analysis revealed that both p50 and p65 proteins contribute to induction of Bf by TNF-α. An I-κB dominant negative mutant blocked Bf induction by TNF-α and reduced the synergistic induction by TNF-α and IFN-γ. In addition, the proteasome inhibitor MG132, which blocks NF-κB induction, blocked TNF-α-induced Bf promoter activity and the synergistic induction of Bf promoter activity by TNF-α and IFN-γ. LPS was found to induce Bf promoter activity through the same NF-κB cis-binding site. These findings suggest that a NF-κB cis-binding site between −433 and −423 bp is required for TNF-α responsiveness and for TNF-α- and IFN-γ-stimulated synergistic responsiveness of the Bf gene.

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“…The levels of retinol‐binding protein 4 and transthyretin proteins were reported to decrease with 32 h exposure to IL‐6 in hepatoma HepG2 cells (El‐Saadany et al ., ); however, their further decrease with 72 h exposure was demonstrated in the present human hepatocyte experiment, suggesting a different response to IL‐6 for the two cell types. Although the decrease in the level of retinol‐binding protein 4 or transthyretin mRNA following exposure to IL‐6 has not yet been reported, the decrease in albumin after 72 h may correspond to a decrease in albumin mRNA following exposure of the hepatocyte to IL‐6 (Huang et al ., ). IL‐6 may regulate these gene expressions negatively.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive and temporal analysis of secreted proteins in the medium from IL‐6 exposed human hepatocyte

Nakata

Saitoh²,

Amano³

et al. 2014

Biomedical Chromatography

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We have previously identified intracellular secretory acute phase response (sAPR) proteins in human hepatocytes following interleukin-6 (IL-6) induction by fluorogenic derivatization (FD)-liquid chromatography (LC)-tandem mass spectrometry (MS/MS). In this report, we utilized this method, which uses 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide (DAABD-Cl) as the FD reagent, to comprehensively and time-dependently analyze secreted proteins in the medium, including sAPR proteins. Since DAABD-Cl selectively reacts with thiol moieties of cysteinyl residues, direct derivatization, high-resolution LC separation and identification of the secreted proteins in the culture medium were successfully achieved without a pretreatment step. As a result, 14 sAPR proteins were identified simultaneously during a 72 h induction by IL-6. The secretion levels of 11 proteins increased, whereas the secretion levels of three important transport proteins decreased (albumin, retinol-binding protein 4 and transthyretin). In addition, the secretion level of a haptoglobin was found to increase significantly between 0 and 6 h by 1.88-fold compared with the control sample. The secretion levels of four cytoplasmic proteins increased: LDH, a known marker for cell damage, and GSTA1, FABP1 and ADH1B, which are marker proteins for hepatocellular damage. The secretion levels of the other two newly identified cytoplasmic proteins, profilin-1 and SOD2, were also found to increase, suggesting that these two proteins represent novel markers for cell damage. These results suggest that the FD-LC-MS/MS proteomics method can be used to analyze comprehensively and time-dependently the secreted proteins and thereby can offer information that aids our understanding of the dynamics of protein secretion affected by the exposure of cytokines such as IL-6.

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Interleukin-6 down-regulates expressions of the aldolase B and albumin genes through a pathway involving the activation of tyrosine kinase

Cited by 35 publications

References 36 publications

Chronic Spontaneous Urticaria Is Characterized by Lower Serum Advanced Glycation End-Products

Chronic Spontaneous Urticaria Is Characterized by Lower Serum Advanced Glycation End-Products

Complement Factor B Gene Regulation: Synergistic Effects of TNF-α and IFN-γ in Macrophages

Comprehensive and temporal analysis of secreted proteins in the medium from IL‐6 exposed human hepatocyte

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