Feline serum amyloid A protein as an endogenous Toll-like receptor 4 agonist

Serum amyloid A (SAA) is one of the major acute phase proteins and a biomarker of infection or inflammation in humans and cats. In humans, cytokine-like functions of SAA protein have been determined, and SAA is considered to be an important factor in immune responses. However, there are no reports about the functions of SAA protein in cats. In the present study, the functions of feline SAA protein on peripheral monocytes were investigated by using TNF-α production as an indicator. In feline peripheral blood monocytes, SAA protein stimulated the transcription of TNF-α within 2h and induced TNF-α secretion in time- and dose-dependent manners. The production of TNF-α by SAA stimulation in feline monocytes was found to be mediated by the activation of nuclear factor-kappa B (NF-κB). Moreover, SAA-stimulated TNF-α production was prevented by a Toll-like receptor 4 (TLR4) antagonist. On the basis of these results, feline SAA was demonstrated to be an endogenous agonist of TLR4 for the stimulation of TNF-α production and secretion by peripheral monocytes. These results suggest that feline SAA can play an important role in the regulation of inflammation and immune responses as it does in humans.