scholarly journals Toll-like Receptors from the Perspective of Cancer Treatment

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 297 ◽  
Author(s):  
Nasir Javaid ◽  
Sangdun Choi
Keyword(s):  
Pattern Recognition ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Toll Like Receptors ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Multiple Signaling ◽  
Anticancer Drug Discovery

Toll-like receptors (TLRs) represent a family of pattern recognition receptors that recognize certain pathogen-associated molecular patterns and damage-associated molecular patterns. TLRs are highly interesting to researchers including immunologists because of the involvement in various diseases including cancers, allergies, autoimmunity, infections, and inflammation. After ligand engagement, TLRs trigger multiple signaling pathways involving nuclear factor-κB (NF-κB), interferon-regulatory factors (IRFs), and mitogen-activated protein kinases (MAPKs) for the production of various cytokines that play an important role in diseases like cancer. TLR activation in immune as well as cancer cells may prevent the formation and growth of a tumor. Nonetheless, under certain conditions, either hyperactivation or hypoactivation of TLRs supports the survival and metastasis of a tumor. Therefore, the design of TLR-targeting agonists as well as antagonists is a promising immunotherapeutic approach to cancer. In this review, we mainly describe TLRs, their involvement in cancer, and their promising properties for anticancer drug discovery.

scholarly journals Bacteroides fragilis Enterotoxin Induces Intestinal Epithelial Cell Secretion of Interleukin-8 through Mitogen-Activated Protein Kinases and a Tyrosine Kinase-Regulated Nuclear Factor-κB Pathway

2004 ◽  
Vol 72 (10) ◽  
pp. 5832-5839 ◽  
Author(s):  
Shaoguang Wu ◽  
Jan Powell ◽  
Nes Mathioudakis ◽  
Sheryl Kane ◽  
Ellen Fernandez ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Protein Kinases ◽  
Bacteroides Fragilis ◽  
Nuclear Factor Κb ◽  
Interleukin 8 ◽  
Biologically Active ◽  
Nuclear Factor ◽  
Intestinal Epithelial ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

ABSTRACT Enterotoxigenic Bacteroides fragilis (ETBF) secretes a 20-kDa metalloprotease toxin termed B. fragilis toxin (BFT). ETBF disease in animals is associated with an acute inflammatory response in the intestinal mucosa, and lethal hemorrhagic colitis may occur in rabbits. In this study, we confirmed recent reports (J. M. Kim, Y. K. Oh, Y. J. Kim, H. B. Oh, and Y. J. Cho, Clin. Exp. Immunol. 123:421-427, 2001; L. Sanfilippo, C. K. Li, R. Seth, T. J. Balwin, M. J. Menozzi, and Y. R. Mahida, Clin. Exp. Immunol. 119:456-463, 2000) that purified BFT stimulates interleukin-8 (IL-8) secretion by human intestinal epithelial cells (HT29/C1 cells) and demonstrate that stimulation of IL-8 production is dependent on biologically active BFT and independent of serum. Induction of IL-8 mRNA expression occurs rapidly and ceases by 6 h after BFT treatment, whereas IL-8 secretion continues to increase for at least 18 h. Our data suggest that BFT-stimulated IL-8 secretion involves tyrosine kinase-dependent activation of nuclear factor-κB (NF-κB) as well as activation of the mitogen-activated protein kinases (MAPKs), p38 and extracellular signal-related kinase. Simultaneous activation of NF-κB and MAPKs appears necessary for secretion of IL-8 by HT29/C1 cells treated with BFT.

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