Expression of Toll-like Receptors (TLRs) and Nucleotide-binding Oligomerization Domain (NODs) in murine peritoneal macrophages on in vitro treatment with Thymosin α 1

Thymosin α 1 (Tα1) treatment of murine peritoneal macrophages in vitro induces the expression of TLRs and Nod2 proteins. Enhanced expressions of TLR2, -4, -5, -6, -7, -8, -9 and Nod2 were observed by RT-PCR and western blotting. Expression of downstream signaling molecules - MyD88, IRAK1, TRAF6, IRF3 were also up regulated on treatment with Tα1. It was also observed that pretreatment of macrophages with pharmacological inhibitors strongly down regulated the Tα1 induced expression of TLR2,-4,-9. Macrophages pretreated with Tα1 and then incubated with ligands for TLRs - Zymosan A, LPS and CpG DNA, showed significantly enhanced production of proinflammatory cytokines, than the macrophages treated with ligands alone. This suggests that pretreatment of macrophages with Tα1 makes them functionally more responsive to further challenge with TLR ligands.