SPA4 peptide is a TLR4 interacting peptide identified from the interface of the surfactant protein-A (SP-A) -TLR4 complex. The interaction between SP-A and TLR4 is important for host defence and SPA4 peptide binding to the activated TLR4 complex suppresses inflammatory responses, inhibiting mRNA and cellular protein levels of pro-interleukin-1beta, caspase activity and release of interleukin-1beta, without affecting TLR4-induced uptake, processing, and clearance of ligands and pathogens. SPA4 peptide does not bind to the natural TLR4 ligand, LPS, or gram-negative bacteria directly. Intraperitoneally and intratracheally administered SPA4 peptide reduces inflammation, bacterial burden, and associated lung injury in mouse models of LPS induced lung inflammation and pseudomonas aeruginosa induced lung infection.
