Premium
Lipopolysaccharide induces TREM‐1‐dependent HIF‐1α expression in human keratinocyte cell line
Author(s) -
Tu Chen,
Wang Shuang,
Hu Xiao,
Wang Wenju,
Dong Yingying,
Xiao Shengxiang,
Wang Xiaopeng
Publication year - 2016
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10693
Subject(s) - hacat , wortmannin , protein kinase b , pi3k/akt/mtor pathway , hypoxia inducible factors , signal transduction , gene silencing , western blot , microbiology and biotechnology , cancer research , biology , chemistry , cell culture , biochemistry , genetics , gene
Abstract 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‐1α (HIF‐1α), subunit of the transcription factor HIF‐1, has participated in angiogenesis and inflammation in psoriasis. Increased expressions of TREM‐1 and HIF‐1α are associated with the infection of microbial pathogens. However, the association between TREM‐1 and HIF‐1α still needs to be elucidated. Results of immunofluorescence showed an overexpression of TREM‐1 and HIF‐1α in HaCaT keratinocytes exposed to 1 µg/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‐1α. Furthermore, the PI3 K inhibitor wortmannin effectively blocked the increased level of HIF‐1α induced by LPS. However, there was no significant change in LPS‐induced expression of TREM‐1. Expressions of TREM‐1, HIF‐1α, and phosphorylated Akt proteins were further examined by real‐time PCR and Western blot, respectively. Our data suggest that TREM‐1 and HIF‐1α 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‐1α in HaCaT cells through the PI3 K/Akt pathway. Our study provides new insights into the possible mechanism of TREM‐1 and HIF‐1α in psoriasis.