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Gardiquimod Inhibits the Expression of Calcium-Induced Differentiation Markers in HaCaT Cells

Bo Jia, Xin Luo, Feng-Wei Cheng, Lei Li, Dao-Jun Hu, Fang Wang, Sheng-Quan Zhang

Mol Biol Rep. 2013 Nov;40(11):6363-9.

PMID: 24057248

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP1020412434 Gardiquimod Gardiquimod 1020412-43-4 Price
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