title: Platelet factor 4 inhibits IL-17/Stat3 pathway via upregulation of SOCS3 expression in melanoma.
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 × 10(6)/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.
authors.affiliation: Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Jinzhou Road 136#, Xiangyang, 441053, Hubei, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Fang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Qiushi
authors.initials: Q
authors.lastname: Sun
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.forename: Huixiong
authors.initials: H
authors.lastname: Qi
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010978:Platelet Factor 4 / Q000494:pharmacology* / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D020381:Interleukin-17; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D010978:Platelet Factor 4