title: Lipopolysaccharide induces TREM-1-dependent HIF-1α expression in human keratinocyte cell line.
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.
authors.affiliation: Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Tu
authors.affiliation: Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Dermatology, Second Affiliated Hospital of Lanzhou University, Lanzhou, Gansu, 730030, China.
authors.forename: Wenju
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Department of Dermatology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D000077191:Wortmannin; C408842:TREM1 protein, human
keywords: HIF-1α; HaCaT cell line; LPS; PI3 K/Akt; TREM-1; psoriasis