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RNA released from necrotic keratinocytes upregulates intercellular adhesion molecule-1 expression in melanocytes

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Abstract

Intercellular adhesion molecule-1 (ICAM-1) expression has been detected in melanocytes around active vitiligo patches as well as in surgically transplanted melanocytes. However, it is unclear whether and how skin injury induces the inappropriate expression of ICAM-1 and other proinflammatory genes in melanocytes. We previously reported that human melanocytes expressed TLR3. We hypothesized that the TLR3 expressed in melanocytes may recognize skin injury by binding to the endogenous ligands secreted by the damaged keratinocytes. Here we showed that RNA released from necrotic keratinocytes induced the upregulation of ICAM-1 protein and mRNA, as shown by FACS and real-time RT-PCR. Use of NF-κB inhibitor prevents upregulation of ICAM-1 in melanocytes indicating a direct role of NF-κB in necrotic keratinocyte-mediated upregulation of ICAM-1. Using a shRNA-expressing lentivirus, we demonstrated that in human melanocytes, TLR3 seems to be necessary for the upregulation of ICAM-1. Using oligonucleotide microarray, we demonstrated a dramatic increase in proinflammatory cytokine and chemokine transcripts (CXCL10, CXCL11, TNFSF10, CCL5, CCL4, CCL2, IFNB1, CCL20, IL-8, and CCL11). These observations suggested that RNA released from necrotic keratinocytes might act as an endogenous TLR3 ligand for the stimulation of ICAM-1 and other proinflammatory gene expression in human melanocytes, which might be involved in the pathogenesis of vitiligo following skin physical trauma.

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Authors and Affiliations

  1. Experimental Research Center, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, 200031, China

    Shujie Zhang

  2. Department of Clinical Laboratory, Taizhou Municipal Hospital, Taizhou, 318000, China

    Shuangchun Liu

  3. Department of Dermatology, Shanghai Skin Disease Hospital, 200 Wuyi Road, Shanghai, 200050, China

    Ning Yu

  4. Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Leihong Xiang

Authors
  1. Shujie Zhang
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  2. Shuangchun Liu
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  3. Ning Yu
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  4. Leihong Xiang
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Corresponding author

Correspondence to Ning Yu.

Additional information

S. Zhang and S. Liu contributed equally to this work.

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Zhang, S., Liu, S., Yu, N. et al. RNA released from necrotic keratinocytes upregulates intercellular adhesion molecule-1 expression in melanocytes. Arch Dermatol Res 303, 771–776 (2011). https://doi.org/10.1007/s00403-011-1170-8

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  • DOI: https://doi.org/10.1007/s00403-011-1170-8

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