Peptidoglycans Promotes Human Leukemic THP-1 Cell Apoptosis and Differentiation

  • Wang, Di (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Xiao, Pei-Ling (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Duan, Hua-Xin (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Zhou, Ming (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Liu, Jin (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Li, Wei (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Luo, Ke-Lin (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Chen, Jian-Jun (Department of Hematolgy and Oncology, Hunan Provincial People's Hospital) ;
  • Hu, Jin-Yue (Central Laboratory, Renmin Hospital, Wuhan University)
  • Published : 2012.12.31


The innate immune system coordinates the inflammatory response to pathogens. To do so, its cells must discriminate self from non-self utilizing receptors that identify molecules synthesized exclusively by microbes. Toll-like receptors have a crucial role in the detection of microbial infection in mammals and insects. In mammals, they have evolved to recognize conserved products unique to microbial metabolism. These include lipopolysaccharide (LPS), lipotechoic acids, and peptidoglycans (PGN). We show here that TLRs, including TLR2, are expressed on the THP-1 human leukemia cell line. Activation of TLR2 signaling in THP-1 by PGN induces the synthesis of various soluble factors and proteins including interleukin-$1{\beta}$, interleukin-8 and TNF-${\alpha}$ and apoptosis of THP-1 with PGN dose and time dependence. Moreover, in this study we show that PGN induces apoptosis of THP-1 cells in a TNF-${\alpha}$-dependent manner. These findings indicate that TLR2 signaling results in a cascade leading to tumor apoptosis and differentiation, which may suggest new clinical prospects using TLR2 agonists as cytotoxic agents in certain cancers.


TLR2;PGN;apoptosis;differentiation;leukemia cell line


Supported by : National Natural Science Foundation of China


  1. Aderem, A (2001). Role of Toll-like receptors in inflammatory response in macrophages. Crit Care Med, 29, S16-8.
  2. Baldridge JR, McGowan P, Evans JT, et al (2004). Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents. Expert Opin Biol Ther, 4, 1129-38.
  3. Blander JM, Medzhitov R (2006). Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature, 440, 808-12.
  4. Bsibsi M, Nomden A, van Noort JM, et al (2012). Tolllike receptor 2 and 3 agonists differentially affect ologodendrocyte survival , differentiation, and myelin membrane formation. J Neurosci Res, 90, 388-98.
  5. Bunting RA, Duffy KE, Lamb RJ, et al (2011). Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo and in vitro. Cell Immunol, 267, 9-16.
  6. El Andaloussi A, Sonabend AM, Han Y, et al (2006). Stimulation of TLR9 with CpG ODN enhances apoptosis of glioma and prolongs the survival of mice with experimental brain tumors. Glia, 54, 526-35.
  7. Hermans IF, Silk JD, Gileadi U, et al (2007). Dendritic cell function can be modulated through cooperative action of TLR ligands and invariant NKT cells. J Immunol, 178, 2721-29.
  8. Jahrsdorfer B, Wooldridge JE, Blackwell SE, et al (2005). B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides. Clin Cancer Res, 11, 1490-99.
  9. Li N, Quidgley Mc, Kobeissy FH, et al (2012). Microbial cell components induced tolerance to flagellin-stimulated inflammation through Toll-like receptor pathways in in testinal epithelial cells. Cytokine, 60, 806-11.
  10. Negishi H, Yanai H, Nakajima A, (2012). Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol, 13, 659-66.
  11. Paone A, Starace D, Galli R, et al (2008). Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-alpha-dependent mechanism. Carcinogenesis, 29, 1334-42.
  12. Peng G, Guo Z, Kiniwa Y, et al (2005). Toll-like receptor 8 mediated-reversal of CD4+ regulatory T cell function. Science, 309, 1380-84.
  13. Rakhesh M, Cate M, Vijay R, et al (2012). A TLR4-interacting peptide inhibits lipopolysaccharide-stimulated inflammatory response, migration and invasion of colon cacer SW480. Oncoimmunology, 1, 1495-506.
  14. Roses RE, Xu M, Koshi GK, et al (2008). Radiation therapy and Toll-like receptor signaling: implication for treatment of cancer. Oncegene, 27, 200-7.
  15. Salaun B, Coste I, Rissoan MC, et al(2006). TLR3 can directly trigger apoptosis in human cancer cells. J Immunol, 176, 4894-901.
  16. Stockfleth E, Trefzer U, Garcia-Bartels C, et al (2003). The use of Toll-like receptor-7 agonist in the treatment of basal cell carcinoma: an overview. Br J Dermatol, 149, 53-6.
  17. Tabiasco J, Devevre E, Rufer N, et al (2006). Human effector CD8+ T lyphocytes express TLR3 as a functional coreceptor. J Immunol, 177, 8708-13.
  18. Takaoka A, Yanai H, Kondo S, et al (2005). Integral role of IRF-5 in the gene induction programme activated by Toll-like recpors. Nature, 434, 243-49.
  19. Wang ZD, Qiao YL, Tian XF, et al (2012). Toll-like receptor 5 agonism protects mice from radiation pneumotis and pulmonary fibrosis. Asian Pac J Cancer Prev, 13, 4763-7.
  20. Wille-Reece U, Flynn BJ, Lore K, et al (2005). HIV Gap protein conjugated to a Toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in nonhuman primates. Proc Natl Acad Sci USA, 102, 15190-94.
  21. Zoglmeier C, Bauer S, Norenberg D, CJ, et al (2011). CpG blocks immunosuppression by myeloid-derived suppressor cells in tumor-bearing mice. Clin Cancer Res, 17, 1765-75.
  22. Zughaier SM (2011). Neisseria meningitides capsular polysaccharides induces inflammatory responses via TLR2 and TLR4-MD-2. J Leukoc Biol, 89, 469-80.

Cited by

  1. TLR9 Expression in Uterine Cervical Lesions of Uyghur Women Correlate with Cervical Cancer Progression and Selective Silencing of Human Papillomavirus 16 E6 and E7 Oncoproteins in Vitro vol.15, pp.14, 2014,