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Platelet Factor 4 Inhibits IL-17/Stat3 Pathway via Upregulation of SOCS3 Expression in Melanoma

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Abstract

Platelet factor 4 (PF4) was the first discovered CXC chemokine and is found in platelet granules at very high concentration. Now, it is becoming increasingly evident that PF4 actively participates in inflammation and immune response. Recent paper demonstrated that PF4 limits the development and response of the Th17 cells and assisted in regulatory T cell development in transplantation. But, the immunoregulatory role of PF4 in tumor has little known and needs to be further investigated. In our current study, wild-type mice are inoculated with melanoma cell line B16-F10 (1 × 106/mouse) and treated with PF4. PF4 inhibits B16 tumor growth and decreases γδ cell infiltration. The expression of interleukin (IL)-17, IL-6, and p-signal transducer and activator of transcription-3 (Stat3) was markedly decreased with treatment of PF4 compared with control in vivo and in vitro. And, the suppressed tumor growth induced by PF4 is abolished by additional treatment of recombinant mouse IL (rmIL)-17. PF4 also induces suppressor of cytokine signaling 3 (SOCS3) upregulations, and PF4 fails to suppress expression of p-Stat3, IL-17, and IL-6 in cells transfected with SOCS3 short interfering RNA (siRNA). In conclusion, PF4 inhibits IL-17/Stat3 pathway via upregulation of SOCS3 expression and may contribute to suppressing tumor growth in murine models of melanoma.

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Authors and Affiliations

  1. Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Jinzhou Road 136#, Xiangyang, 441053, Hubei, China

    Shanshan Fang, Bo Liu, Qiushi Sun, Juan Zhao, Huixiong Qi & Quan Li

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  1. Shanshan Fang
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  2. Bo Liu
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  3. Qiushi Sun
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  4. Juan Zhao
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  5. Huixiong Qi
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  6. Quan Li
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Correspondence to Quan Li.

Additional information

Bo Liu and Shanshan Fang contributed equally to this paper.

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Fang, S., Liu, B., Sun, Q. et al. Platelet Factor 4 Inhibits IL-17/Stat3 Pathway via Upregulation of SOCS3 Expression in Melanoma. Inflammation 37, 1744–1750 (2014). https://doi.org/10.1007/s10753-014-9903-4

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  • DOI: https://doi.org/10.1007/s10753-014-9903-4

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