Abstrakt

A key receptor in apoptosis: Toll-like receptor 3 (TLR3).

Asuman Deveci Ozkan, Humeyra Nur Kaleli and Suleyman Kaleli

The mammals have two types of immune system as innate and acquired immunity. The innate immune system initiates inflammatory response as well as phagocytosis to microbial attack, thus forming the organism's first line of protection. This inflammatory response is the result of induction of pattern recognition receptors (PRRs) which is inherited in the organism. TLRs are the best defined receptors among the PRRs. TLR3 is activated by double-stranded RNA/polyinosinic–polycytidylic acid (dsRNA, poly (I:C)). TRIF protein plays a role as an adaptor protein in TLR3 signaling pathway. The dsRNA-induced apoptosis by the ligand of TLR3 requires activation of RIP1, caspase-3 and caspase-8. While TLR3 signaling can contribute to the eradication of tumors with the RIP-1/FADD pathway, it increases the activation of IFN-α, IFN-β and NK cells and it also leads to the formation of pro-angiogenic factors that contribute to tumor progression through NF-κB activation. TLR3 stimulation with dsRNA is considered directly promoting tumor cell apoptosis in many types of cancer such as breast, melanoma, prostate, cervical, colon and hepatocellular carcinoma. It is known that poly (I:C) is directly cause apoptosis in cancer cells by caspase-dependent pathway. It has also been shown that certain NF-κB proteins are required for TLR3-mediated apoptosis. Because of its high toxicity, Poly (I:C) cannot be used in chemotherapy. Studies have shown that dsRNA induces apoptosis by caspase-dependent manner but there is no clear evidence of how TLR3 plays a role in dsRNA-mediated apoptosis. The molecular mechanism of TLR3-mediated apoptosis needs to be fully understood.