Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages

  • Authors:
    • Chenchen Zhang
    • Yaxin Bi
    • Guoxi Jin
    • Huaiyong Gan
    • Lei Yu
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233020, P.R. China, Department of Pathology, Bengbu Medical College, Bengbu, Anhui 233020, P.R. China
  • Pages: 2715-2720
    |
    Published online on: May 7, 2015
       https://doi.org/10.3892/mmr.2015.3753
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Macrophages are involved in the progression of atherosclerosis by releasing pro‑inflammatory cytokines. High levels of interleukin (IL)‑18 are associated with an increased risk of developing diabetes and atherosclerosis. The present study aimed to investigate the association between IL‑18, and high and fluctuating glucose levels in mouse peritoneal macrophages (MPMs), and to assess the involvement of the c‑Jun N‑terminal kinase (JNK) pathway in this association. The MPMs were exposed to 4, 8, 16, 24 and 32 mM glucose for 6 h, which was alternated to either 4/24 mM glucose every 1.5 h for 6 h, or to 32 mM glucose for 3, 6, 12 and 18 h. The expression and secretion levels of IL‑18 were detected using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and ELISA, respectively. High levels of glucose increased the expression and secretion levels of IL‑18 in a dose‑dependent manner (P<0.05, vs. 4 mM glucose). This increase was more important in the cells exposed to fluctuating 4/24 mM glucose every 1.5 h compared with the cells exposed to stable 24 mM glucose (RT‑qPCR, 0.78±0.05, vs. 0.66±0.07; ELISA, 188.23±20.32, vs. 143.16±13.07 pg/ml; P<0.05). The expression and secretion levels of IL‑18 increased 8 and 12 h following exposure to high‑glucose, and then decreased at 18 h (P<0.05, vs. 3 h). Furthermore, SP600125, a JNK inhibitor, decreased the high‑glucose‑induced gene expression of IL‑18 in a dose‑dependent manner. Therefore, high and fluctuating levels of glucose may be associated with inflammation and diabetic atherosclerosis by regulating the expression levels of IL‑18. The present study identified the JNK signaling pathway as one of the mechanisms underlying this association. Targeting IL‑18 may be a novel therapeutic approach against diabetes‑associated atherosclerosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Kannel WB and McGee DL: Diabetes and cardiovascular disease. The Framingham study. JAMA. 241:2035–2038. 1979. View Article : Google Scholar : PubMed/NCBI

2 

Haffner SM, Lehto S, Rönnemaa T, et al: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 339:229–234. 1998. View Article : Google Scholar : PubMed/NCBI

3 

Hansson GK: Inflammation, atherosclerosis and coronary artery disease. N Engl J Med. 352:1685–1695. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Shalhoub J, Falck-Hansen MA, Davies AH and Monaco C: Innate immunity and monocyte-macrophage activation in atherosclerosis. J Inflamm (Lond). 8:92011. View Article : Google Scholar

5 

Formigli L, Manneschi LI, Nediani C, et al: Are macrophages involved in early myocardial reperfusion injury? Ann Thorac Surg. 71:1596–1602. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Herskowitz A, Choi S, Ansari AA and Wesselingh S: Cytokine mRNA expression in postischemic/reperfused myocardium. Am J Pathol. 146:419–428. 1995.PubMed/NCBI

7 

Lotz M: Interleukin-6. Cancer Invest. 11:732–742. 1993. View Article : Google Scholar : PubMed/NCBI

8 

Wen Y, Gu J, Li SL, et al: Elevated glucose and diabetes promote interleukin-12 cytokine gene expression in mouse macrophages. Endocrinology. 147:2518–2525. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Nakanishi K, Yoshimoto T, Tsutsui H and Okamura H: Interleukin-18 is a unique cytokine that stimulates both Th1 and Th2 responses depending on its cytokine milieu. Cytokine Growth Factor Rev. 12:53–72. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Hoshino T, Kawase Y, Okamoto M, et al: Cutting edge: IL-18-transgenic mice: in vivo evidence of a broad role for IL-18 in modulating immune function. J Immunol. 166:7014–7018. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Pope RM and Tschopp J: The role of interleukin-1 and the inflammasome in gout: implications for therapy. Arthritis Rheum. 56:3183–3188. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Hoshino K, Tsutsui H, Kawai T, et al: Cutting edge: generation of IL-18 receptor-deficient mice: evidence for IL-1 receptor-related protein as an essential IL-18 binding receptor. J Immunol. 162:5041–5044. 1999.PubMed/NCBI

13 

Tsutsui H, Nakanishi K, Matsui K, et al: IFN-gamma-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. J Immunol. 157:3967–3973. 1996.PubMed/NCBI

14 

Esposito K, Pontillo A, Ciotola M, et al: Weight loss reduces interleukin-18 levels in obese women. J Clin Endocrinol Metab. 87:3864–3866. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Hung J, McQuillan BM, Chapman CM, et al: Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler Thromb Vasc Biol. 25:1268–1273. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Escobar-Morreale HF, Botella-Carretero JI, Villuendas G, et al: Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity. J Clin Endocrinol Metab. 89:806–811. 2004. View Article : Google Scholar : PubMed/NCBI

17 

Fischer CP, Perstrup LB, Berntsen A, et al: Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans. Clin Immunol. 117:152–160. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Thorand B, Kolb H, Baumert J, et al: Elevated levels of interleukin-18 predict the development of type 2 diabetes: results from the MONICA/KORA Augsburg Study, 1984–2002. Diabetes. 54:2932–2938. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Yamaoka-Tojo M, Tojo T, Wakaume K, et al: Circulating interleukin-18: A specific biomarker for atherosclerosis-prone patients with metabolic syndrome. Nutr Metab (Lond). 8:32011. View Article : Google Scholar

20 

Blankenberg S, Tiret L, Bickel C, et al: Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation. 106:24–30. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Tiret L, Godefroy T, Lubos E, et al: Genetic analysis of the interleukin-18 system highlights the role of the interleukin-18 gene in cardiovascular disease. Circulation. 112:643–650. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Hansen AP and Johansen K: Diurnal patterns of blood glucose, serum free fatty acids, insulin, glucagon and growth hormone in normals and juvenile diabetics. Diabetologia. 6:27–33. 1970. View Article : Google Scholar : PubMed/NCBI

23 

Monnier L, Mas E, Ginet C, et al: Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 295:1681–1687. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Chang CM, Hsieh CJ, Huang JC and Huang IC: Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus. Acta Diabetol. 49:S171–S177. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Node K and Inoue T: Postprandial hyperglycemia as an etiological factor in vascular failure. Cardiovasc Diabetol. 8:232009. View Article : Google Scholar : PubMed/NCBI

26 

Rizzo MR, Barbieri M, Marfella R and Paolisso G: Reduction of oxidative stress and inflammation by blunting daily acute glucose fluctuations in patients with type 2 diabetes: role of dipeptidyl peptidase-IV inhibition. Diabetes Care. 35:2076–2082. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Azuma K, Kawamori R, Toyofuku Y, et al: Repetitive fluctuations in blood glucose enhance monocyte adhesion to the endothelium of rat thoracic aorta. Arterioscler Thromb Vasc Biol. 26:2275–2280. 2006. View Article : Google Scholar : PubMed/NCBI

28 

Sun J, Xu Y, Dai Z and Sun Y: Intermittent high glucose stimulate MCP-l, IL-18 and PAI-1, but inhibit adiponectin expression and secretion in adipocytes dependent of ROS. Cell Biochem Biophys. 55:173–180. 2009. View Article : Google Scholar

29 

Gill R, Tsung A and Billiar T: Linking oxidative stress to inflammation: Toll-like receptors. Free Radic Biol Med. 48:1121–1132. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Davis RJ: Signal transduction by the JNK group of MAP kinases. Cell. 103:239–252. 2000. View Article : Google Scholar : PubMed/NCBI

31 

Kim YM, Im JY, Han SH, et al: IFN-gamma up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages. J Immunol. 165:3198–3205. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Mallat Z, Corbaz A, Scoazec A, et al: Interleukin-18/interleukin-18 binding protein signaling modulates atherosclerotic lesion development and stability. Circ Res. 89:E41–E45. 2001. View Article : Google Scholar : PubMed/NCBI

33 

Everett BM, Bansal S, Rifai N, et al: Interleukin-18 and the risk of future cardiovascular disease among initially healthy women. Atherosclerosis. 202:282–288. 2009. View Article : Google Scholar :

34 

Arndt PG, Fantuzzi G and Abraham E: Expression of interleukin-18 in the lung after endotoxemia or hemorrhage-induced acute lung injury. Am J Respir Cell Mol Biol. 22:708–713. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Esposito K, Nappo F, Marfella R, et al: Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation. 106:2067–2072. 2002. View Article : Google Scholar : PubMed/NCBI

36 

Kim YM, Kang HS, Paik SG, et al: Roles of IFN consensus sequence binding protein and PU. 1 in regulating IL-18 gene expression. J Immunol. 163:2000–2007. 1999.PubMed/NCBI

37 

Alsaleh G, Suffert G, Semaan N, et al: Bruton’s tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes. J Immunol. 182:5088–5097. 2009. View Article : Google Scholar : PubMed/NCBI

38 

Cordoba-Rodriguez R, Fang H, Lankford CS and Frucht DM: Anthrax lethal toxin rapidly activates caspase-1/ICE and induces extracellular release of interleukin (IL)-1beta and IL-18. J Biol Chem. 279:20563–20566. 2004. View Article : Google Scholar : PubMed/NCBI

39 

Zhu J, Krishnegowda G and Gowda DC: Induction of proinflammatory responses in macrophages by the glycosylphosphatidylinositols of Plasmodium falciparum: the requirement of extracellular signal-regulated kinase, p38, c-Jun N-terminal kinase and NF-kappaB pathways for the expression of proinflammatory cytokines and nitric oxide. J Biol Chem. 280:8617–8627. 2005. View Article : Google Scholar

40 

Yun W and Li C: JNK pathway is required for TNCB-induced IL-18 expression in murine keratinocytes. Toxicol In Vitro. 24:1064–1069. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang C, Bi Y, Jin G, Gan H and Yu L: High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages. Mol Med Rep 12: 2715-2720, 2015.
APA
Zhang, C., Bi, Y., Jin, G., Gan, H., & Yu, L. (2015). High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages. Molecular Medicine Reports, 12, 2715-2720. https://doi.org/10.3892/mmr.2015.3753
MLA
Zhang, C., Bi, Y., Jin, G., Gan, H., Yu, L."High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages". Molecular Medicine Reports 12.2 (2015): 2715-2720.
Chicago
Zhang, C., Bi, Y., Jin, G., Gan, H., Yu, L."High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages". Molecular Medicine Reports 12, no. 2 (2015): 2715-2720. https://doi.org/10.3892/mmr.2015.3753
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang C, Bi Y, Jin G, Gan H and Yu L: High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages. Mol Med Rep 12: 2715-2720, 2015.
APA
Zhang, C., Bi, Y., Jin, G., Gan, H., & Yu, L. (2015). High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages. Molecular Medicine Reports, 12, 2715-2720. https://doi.org/10.3892/mmr.2015.3753
MLA
Zhang, C., Bi, Y., Jin, G., Gan, H., Yu, L."High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages". Molecular Medicine Reports 12.2 (2015): 2715-2720.
Chicago
Zhang, C., Bi, Y., Jin, G., Gan, H., Yu, L."High and fluctuating glucose levels increase the expression and secretion of interleukin‑18 in mouse peritoneal macrophages". Molecular Medicine Reports 12, no. 2 (2015): 2715-2720. https://doi.org/10.3892/mmr.2015.3753
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team