Gardiquimod inhibits the expression of calcium-induced differentiation markers in HaCaT cells.
Toll-like receptor 7 (TLR7) is an important member in pattern recognition receptors families. TLR7 signal pathway is involved in the physiological process in many type cells, but the impact of TRL7 on differentiation in the human keratinocytes is still unknown. In this study, we investigated the expression of TLR7 in keratinocytes, and the effect of TLR7 agonist gardiquimod on the expression of calcium (Ca(2+))-induced keratinocytes differentiation markers in HaCaT cells. Immunohistochemistry and western-blotting analysis showed that TLR7 is expressed in basal keratinocytes of normal skin and in the human keratinocyte cell line HaCaT, but not expressed in the keratinocytes of psoriasis lesions. Pretreatment with gardiquimod could down-regulate Ca(2+)-induced differentiation marker expression and activate Raf-MEK-ERK and PI3K-AKT signal pathways in HaCaT cells. However, specific inhibitors studies showed that the down-regulation of the differentiation markers expression by gardiquimod was not dependent on the activation of these two pathways. TLR7 may play an important role in the pathogenesis of psoriasis through regulating the differentiation of the keratinocytes, and will give a new insight into the psoriasis.
Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui, China.
Bo
B
Jia
Xin
X
Luo
Feng-Wei
FW
Cheng
Lei
L
Li
Dao-Jun
DJ
Hu
Fang
F
Wang
Sheng-Quan
SQ
Zhang
D000634:Aminoquinolines / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000235:genetics*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D053556:Keratin-1 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism
D000634:Aminoquinolines; D000943:Antigens, Differentiation; D007093:Imidazoles; D053556:Keratin-1; D011498:Protein Precursors; D051199:Toll-Like Receptor 7; D051193:Toll-Like Receptors; C546771:gardiquimod; C032253:involucrin; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium