The Role of Toll-like Receptors (TLRs) Mediated Inflammation in Pancreatic Cancer Pathophysiology
Abstract
:1. Introduction
2. Toll-like Receptors
3. Toll-like Receptor 1
4. Toll-like Receptor 2
5. Toll-like Receptor 3
6. Toll-like Receptor 4
7. Toll-like Receptor 5
8. Toll-like Receptor 7
9. Toll-like Receptor 9
10. TLRs Agonists
11. TLRs Antagonists
12. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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TLRs | Localization | PAMPs | Adaptor | Pancreatic Cancer Cell Line | Refs. |
---|---|---|---|---|---|
TLR1 | Plasma membrane | Triacyl lipopeptides | Myd88/TIRAP | Not reported | [19,32] |
TLR2 | Plasma membrane | Lycolipids, lipoprotein, lipoteichoic acid, peptidoglycan, zymosan | Myd88/TIRAP | BxPC-3; MIA PaCa-2, MDA Panc-28, SU 8686, SW-1990, AsPC-1, Panc-1 | [19,33,34,35] |
TLR3 | Endosome | Double-stranded RNA | TRIF | AsPC-1, Colo357, Panc-89, PancTu-1, Pt45P1 | [36,37,38] |
TLR4 | Plasma membrane | Lipopolysaccharide (LPS), heat shock proteins | Myd88/TIRAP | AsPC-1, BxPC-3, CFPAC, MIA PaCa-2, MDA Panc-28, Panc-1, Sw-1990 | [34,35,39] |
TLR5 | Plasma membrane | Flagellin | Myd88 | Not reported | [32] |
TLR6 | Plasma membrane | Diacyl lipopeptides, lipoteichoic acid | Myd88/TIRAP | Not reported | [32] |
TLR7 | Endosome | Single-stranded RNA | Myd88 | Colo357, MIA PaCa-2, MDA Panc-28, Panc-1, Sw-1990, Panc-89, PancTu-1, BxPC-3 | [38,40,41,42] |
TLR8 | Endosome | Single-stranded RNA | Myd88 | Panc-1 | [41] |
TLR9 | Endosome | DNA (CpG) | Myd88 | GER, MIA PaCa-2, MDA Panc-28, Panc-1, Sw-1990, T3M4 | [34,43,44] |
TLR10 | Endosome | Unknown | Unknown | Not reported | [32] |
TLRs | Expression | Pancreatic Cancer Prognosis | Refs. |
---|---|---|---|
TLR1 | High | Favorable | [49] |
TLR2 | High | Favorable | [15] |
Unfavorable | [33,34,35,51] | ||
TLR3 | High | Unfavorable | [36] |
TLR4 | High | Favorable | [15] |
Unfavorable | [39,52,53,54] | ||
TLR5 | High | Unfavorable | [55,56] |
TLR7 | High | Unfavorable | [16,41,57] |
TLR8 | High | Unfavorable | [41,57] |
TLR9 | High | Favorable | [43,58,59,60] |
Unfavorable | [44,61] |
Drug Name | Target | Drug Class | Refs. |
---|---|---|---|
Pam3CSK4 | TLR1/2 | Synthetic triacylated lipopeptide | [119] |
MALP-2 | TLR2/6 | synthetic lipopeptide | [90,91] |
PSK | TLR2 | Protein-bound polysaccharide | [96] |
PAUF | TLR2/4 | Peptide | [103,120] |
SMP-105 | TLR2 | Components of cell wall skeleton isolated from Mycobacterium Bovis | [121] |
CBLB612 | TLR2/6 | Synthetic derivative of mycoplasma lipopeptide | [122] |
Phenylmethimazole (C10) | TLR3 | Methimazole derivative | [36] |
Poly I:C | TLR3 | Synthetic analog of viral dsRNA (polyinosinic-polycytidylic acid) | [123,124] |
PolyICLC | TLR3 | Polyinosinic-polycytidylic acid mixed with the stabilizers carboxymethylcellulose and polylysine | [125] |
Poly-IC12U | TLR3 | Poly I:C derivative with shorter half life and less toxicity | [126] |
IPH 3102 | TLR3 | Synthetic dsRNA agent | [127] |
ARNAX | TLR3 | Synthetic DNA/RNA hybrid molecule | [128] |
MPLA | TLR4 | Lipid A derivative | [129] |
OK-432 | TLR4 | Lyophilized mixture of group A Streptococcus pyogenes | [130] |
AS04 | TLR4 | Combination of MPLA and aluminum salt | [131] |
GLA-SE (G100) | TLR4 | Glucopyranosyl lipid-A oil-in-water emulsion | [132] |
CBLB502 | TLR5 | derivative of Salmonella flagellin | [133] |
M-VM3 (Mobilan) | TLR5 | Recombinant non-replicating adenovirus that directs expression of human Toll-like receptor 5 and of a flagellin derivative that acts as a selective agonist of TLR5 | [134] |
ssRNA40 | TLR7 | 20-mer phosphorothioate protected single-stranded RNA oligonucleotide containing a GU-rich sequence | [16] |
Gardiquimod | TLR7 | Imidazoquinoline compound | [42] |
Resiquimod (R848) | TLR7 | Imidazoquinoline compound | [110] |
Bistriazolyl | TLR7 | Small Molecule | [135] |
VTX1463 | TLR8 | Small Molecule | [136] |
CpG-1826 | TLR9 | Oligodeoxynucleotide containing immunostimulatory CpG motifs | [122] |
CpG-7909 | TLR9 | Oligodeoxynucleotide containing immunostimulatory CpG motifs | [137] |
IMO-2155 | TLR9 | Oligodeoxynucleotide containing immunostimulatory CpG motifs | [138] |
MGN1703 | TLR9 | Covalently closed natural DNA molecule | [139] |
dSLIM | TLR9 | MGN1703 derivative | [140] |
SD-101 | TLR9 | Oligodeoxynucleotide containing immunostimulatory CpG motifs | [141] |
KSK-CpG | TLR9 | Oligodeoxynucleotide containing immunostimulatory CpG motifs | [142] |
ODN2216 | TLR9 | Oligodeoxynucleotide containing immunostimulatory CpG motifs | [143] |
ODN M362 | TLR9 | Oligodeoxynucleotide containing immunostimulatory CpG motifs | [144] |
Drug Name | Target | Drug Class | Refs. |
---|---|---|---|
TAK-242 (Resatorvid) | TLR4 | Small molecule inhibitor | [150] |
CRX-526 | TLR4 | Synthetic lipopolysaccharide | [163] |
CX-01 | TLR4 | heparin-derived olysaccharide | [164] |
CXC195 | TLR4 | tetramethylpyrazine analogue | [165] |
Eritoran (E5564) | TLR4 | Synthetic lipopolysaccharide | [168] |
Atractylenolide-1 | TLR4 | sesquiterpene compound | [169] |
Triptolide | TLR4 | diterpenoid epoxide | [170] |
Paeonol | TLR4 | Small molecule inhibitor | [171] |
NI-0101 | TLR4 | Monoclonal antibody | [172] |
Nalmefene (JKB-121) | TLR4 | Small molecule inhibitor | [173] |
Ibudilast (AV-411, N-166) | TLR4 | Small molecule inhibitor | [174] |
Polymyxin B (PMB) | TLR4 | Cyclic polypeptide antibiotic | [175] |
OPN305 | TLR2 | Monoclonal antibody | [176] |
Hydroxychloroquine | TLR7,9 | Quinolone | [177] |
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Orlacchio, A.; Mazzone, P. The Role of Toll-like Receptors (TLRs) Mediated Inflammation in Pancreatic Cancer Pathophysiology. Int. J. Mol. Sci. 2021, 22, 12743. https://doi.org/10.3390/ijms222312743
Orlacchio A, Mazzone P. The Role of Toll-like Receptors (TLRs) Mediated Inflammation in Pancreatic Cancer Pathophysiology. International Journal of Molecular Sciences. 2021; 22(23):12743. https://doi.org/10.3390/ijms222312743
Chicago/Turabian StyleOrlacchio, Arturo, and Pellegrino Mazzone. 2021. "The Role of Toll-like Receptors (TLRs) Mediated Inflammation in Pancreatic Cancer Pathophysiology" International Journal of Molecular Sciences 22, no. 23: 12743. https://doi.org/10.3390/ijms222312743