Lipopolysaccharide induces TREM-1-dependent HIF-1α expression in human keratinocyte cell line.

Bacterial infection is an important factor that can trigger and exacerbate psoriasis. The protein triggering receptor expressed on myeloid cells type-1 (TREM-1) is overexpressed in psoriasis and decreased after a successful treatment. Hypoxia inducible factor-1 alpha (HIF-1 alpha), subunit of the transcription factor HIF-1, has participated in angiogenesis and inflammation in psoriasis. Increased expressions of TREM-1 and HIF-1 alpha are associated with the infection of microbial pathogens. However, the association between TREM-1 and HIF-1 alpha still needs to be elucidated. Results of immunofluorescence showed an overexpression of TREM-1 and HIF-1 alpha in HaCaT keratinocytes exposed to 1mg/mL of lipopolysaccharide (LPS). Particularly, silencing of TREM-1 expression by siRNA suppressed the inducible effect of LPS on phosphoinositide 3-kinase (PI3 K)/Akt, the critical transduction mediator, and HIF-1 alpha. Furthermore, the PI3K inhibitor wortmannin effectively blocked the increased level of HIF-1 alpha induced by LPS. However, there was no significant change in LPS-induced expression of TREM-1. Expressions of TREM-1, HIF-1 alpha, and phosphorylated Akt proteins were further examined by real-time PCR and Western blot, respectively. Our data suggest that TREM-1 and HIF-1 alpha are expressed on keratinocytes and could be upregulated by bacterial infection. Moreover, LPS-induced TREM-1 has an ability to mediate the expression of HIF-1 alpha in HaCaT cells through the PI3 K/Akt pathway. Our study provides new insights into the possible mechanism of TREM-1 and HIF-1 alpha in psoriasis.