Expression of toll‑like receptor 4 in maternal monocytes of patients with gestational diabetes mellitus

  • Authors:
    • Bao‑Guo Xie
    • Song Jin
    • Wei‑Jie Zhu
  • View Affiliations

  • Published online on: October 24, 2013     https://doi.org/10.3892/etm.2013.1360
  • Pages: 236-240
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Abstract

Toll‑like receptors (TLRs) are pattern recognition receptors and play an important role in innate immune responses and the occurrence of inflammatory disease. TLR4 is a member of the TLR family and its activation is capable of inducing inflammatory responses, reflecting a relationship between the innate and adaptive immune systems. However, whether TLR4 is expressed in patients with gestational diabetes mellitus (GDM) has not been elucidated. The aim of the present study was to investigate whether TLR4 is expressed in maternal peripheral blood monocytes of patients with GDM. A case‑control study, using standard quantitative polymerase chain reaction and western blotting, was performed to assess the TLR4 expression in 30 females with GDM and 32 healthy pregnant females at similar gestational ages. Serum tumor necrosis factor (TNF)‑α levels were assessed using ELISA in all the females. The TLR4 expression levels in the maternal peripheral blood monocytes and the serum TNF‑α levels were increased in females with GDM compared with healthy pregnant females (P<0.05). Additionally, there was a positive correlation between the TLR4 expression level in peripheral blood monocytes and serum TNF‑α levels in all the females. These results indicate that TLR4‑mediated release of inflammatory cytokines may represent one factor leading to increased glucose levels in patients with GDM. In addition, TLR4 may be involved in the pathogenesis of GDM.

References

1 

Metzger BE, Buchanan TA, Coustan DR, et al: Summary and recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus. Diabetes Care. 30:S251–S260. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Xiong X, Saunders L, Wang F and Demianczuk N: Gestational diabetes mellitus: prevalence, risk factors, maternal and infant outcomes. Int J Gynaecol Obstet. 75:221–228. 2001. View Article : Google Scholar : PubMed/NCBI

3 

Landon MB, Spong CY, Thom E, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 361:1339–1348. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Fernández-Real JM and Pickup JC: Innate immunity, insulin resistance and type 2 diabetes. Trends Endocrinol Metab. 19:10–16. 2008.PubMed/NCBI

5 

Greenberg A and McDaniel M: Identifying the links between obesity, insulin resistance and β-cell function: potential role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes. Eur J Clin Invest. 32(Suppl 3): 24–34. 2002.

6 

Medzhitov R: Toll-like receptors and innate immunity. Nat Rev Immunol. 1:135–145. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Hill HR, Hogan NA, Rallison ML, et al: Functional and metabolic abnormalities of diabetic monocytes. Adv Exp Med Biol. 141:621–628. 1982. View Article : Google Scholar : PubMed/NCBI

8 

Kolek MJ, Carlquist JF, Muhlestein JB, et al: Toll-like receptor 4 gene Asp299Gly polymorphism is associated with reductions in vascular inflammation, angiographic coronary artery disease, and clinical diabetes. Am Heart J. 148:1034–1040. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Nitsche JF, Jiang SW and Brost BC: Toll-like receptor-2 and toll-like receptor-4 expression on maternal neutrophils during pregnancy. Am J Reprod Immunol. 64:427–434. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Kajikawa O, Frevert CW, Lin SM, et al: Gene expression of Toll-like receptor-2, Toll-like receptor-4, and MD2 is differentially regulated in rabbits with Escherichia coli pneumonia. Gene. 344:193–202. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H and Flier JS: TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest. 116:3015–3025. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Nguyen MA, Favelyukis S, Nguyen AK, et al: A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem. 282:35279–35292. 2007. View Article : Google Scholar : PubMed/NCBI

13 

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 29(Suppl 1): S43–S48. 2006.

14 

Akira S, Takeda K and Kaisho T: Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol. 2:675–680. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Dasu MR, Devaraj S, Zhao L, Hwang DH and Jialal I: High glucose induces toll-like receptor expression in human monocytes: mechanism of activation. Diabetes. 57:3090–3098. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Zhande R, Dauphinee SM, Thomas JA, Yamamoto M, Akira S and Karsan A: FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. Mol Cell Biol. 27:7394–7404. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Di Benedetto A, Russo G, Corrado F, et al: Inflammatory markers in women with a recent history of gestational diabetes mellitus. J Endocrinol Invest. 28:34–38. 2005.PubMed/NCBI

18 

Devaraj S, Dasu MR, Rockwood J, Winter W, Griffen SC and Jialal I: Increased toll-like receptor (TLR) 2 and TLR4 expression in monocytes from patients with type 1 diabetes: further evidence of a proinflammatory state. J Clin Endocrinol Metab. 93:578–583. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Mohammad MK, Morran M, Slotterbeck B, et al: Dysregulated Toll-like receptor expression and signaling in bone marrow-derived macrophages at the onset of diabetes in the non-obese diabetic mouse. Int Immunol. 18:1101–1113. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Lu YC, Yeh WC and Ohashi PS: LPS/TLR4 signal transduction pathway. Cytokine. 42:145–151. 2008. View Article : Google Scholar

21 

Mullick AE, Tobias PS and Curtiss LK: Toll-like receptors and atherosclerosis: key contributors in disease and health? Immunol Res. 34:193–209. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Schulthess FT, Paroni F, Sauter NS, et al: CXCL10 impairs β cell function and viability in diabetes through TLR4 signaling. Cell Metab. 9:125–139. 2009.

23 

Buchanan TA and Xiang AH: Gestational diabetes mellitus. J Clin Invest. 115:485–491. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Dandona P, Aljada A and Bandyopadhyay A: Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 25:4–7. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Hussey SE, Liang H, Costford SR, et al: TAK-242, a small-molecule inhibitor of Toll-like receptor 4 signalling, unveils similarities and differences in lipopolysaccharide- and lipid-induced inflammation and insulin resistance in muscle cells. Biosci Rep. 33:37–47. 2012. View Article : Google Scholar : PubMed/NCBI

26 

Reyna SM, Ghosh S, Tantiwong P, et al: Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes. 57:2595–2602. 2008. View Article : Google Scholar

27 

Kirwan JP, Hauguel-De Mouzon S, et al: TNF-α is a predictor of insulin resistance in human pregnancy. Diabetes. 51:2207–2213. 2002.

28 

Qureshi M: Avian macrophage and immune response: an overview. Poult Sci. 82:691–698. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Deng S, Wu Q, Yu K, et al: Changes in the relative inflammatory responses in sheep cells overexpressing of toll-like receptor 4 when stimulated with LPS. PLoS One. 7:e471182012. View Article : Google Scholar : PubMed/NCBI

30 

Hotamisligil G: The role of TNFα and TNF receptors in obesity and insulin resistance. J Intern Med. 245:621–625. 1999.

31 

Takeda K and Akira S: TLR signaling pathways. Semin Immunol. 16:3–9. 2004. View Article : Google Scholar

32 

Paik YH, Schwabe RF, Bataller R, Russo MP, Jobin C and Brenner DA: Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology. 37:1043–1055. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Catalano P, Highman T, Huston L and Friedman J: Relationship between reproductive hormones/TNF alpha and longitudinal changes in insulin sensitivity during gestation. Diabetes. 45:175A1996.

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APA
Xie, B., Jin, S., & Zhu, W. (2014). Expression of toll‑like receptor 4 in maternal monocytes of patients with gestational diabetes mellitus. Experimental and Therapeutic Medicine, 7, 236-240. https://doi.org/10.3892/etm.2013.1360
MLA
Xie, B., Jin, S., Zhu, W."Expression of toll‑like receptor 4 in maternal monocytes of patients with gestational diabetes mellitus". Experimental and Therapeutic Medicine 7.1 (2014): 236-240.
Chicago
Xie, B., Jin, S., Zhu, W."Expression of toll‑like receptor 4 in maternal monocytes of patients with gestational diabetes mellitus". Experimental and Therapeutic Medicine 7, no. 1 (2014): 236-240. https://doi.org/10.3892/etm.2013.1360