【Objective】 To investigate the role of triggering receptor expressed on myeloid cells-1 (TREM-1) in Pseudomonas aeruginosa (PA) keratitis and the possible molecular mechanism involved. 【Methods】 To determine the relationship between TREM-1 and PA keratitis

we established the resistant (BALB/c) and susceptible (C57BL/6) PA keratitis murine model

and then examined TREM-1 mRNA and protein levels in the normal and infected corneas of BALB/c and C57BL/6 mice by real-time PCR and immunostaining

respectively. To further explore the mechanism of TREM-1 in PA keratitis

peritoneal M were challenged with lipopolysaccharide (LPS) or live PA

and then TREM-1 expression was tested by real-time PCR. Peritoneal macrophages (M) were pretreated with inhibitors for mitogen activated protein kinases (MAPKs) or phosphatidylinositol 3-kinase (PI3K)

and after challenge with LPS and agonistic mTREM-1 Ab

mRNA levels of pro-inflammatory cytokines including IL-1

MIP-2

TNF

and IL-6 was determined using real-time PCR. TREM-1 mRNA levels were also tested by real-time PCR in peritoneal M pretreated with IFN or IL-4

IL-10. 【Results】 TREM-1 expression levels were significantly increased in C57BL/6 vs BALB/c corneas after PA infection. In peritoneal M

TREM-1 expression was also increased after LPS stimulation or PA infection. TREM-1 modulated pro-inflammatory cytokine production through MAPK and PI3K-Akt signaling pathway. TREM-1 expression levels were significantly increased after stimulation with LPS and Th1 cytokine

but not Th2 cytokine. 【Conclusion】 The PA-induced up-regulation of TREM-1 amplified corneal inflammation by modulating production of Th1 and Th2 cytokines

thereby accelerating the disease progression of PA keratitis. These findings may provide a promising target for treatment of PA keratitis.