%0 Journal Article
%T Polo-Like Kinase 1 (PLK1) Is Involved in Toll-like Receptor (TLR)-Mediated TNF-¦Á Production in Monocytic THP-1 Cells
%A Jinyue Hu
%A Guihua Wang
%A Xueting Liu
%A Lina Zhou
%A Manli Jiang
%A Li Yang
%J PLOS ONE
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0078832
%X Polo-like kinases (PLKs) have been reported to be essential components of anti-viral pathways. However, the role of PLKs in the production of pro-inflammatory cytokines induced by TLR activation is uncertain. We report here that monocytic THP-1 cells expressed PLK1, PLK2, PLK3 and PLK4. When THP-1 cells were treated with GW843682X, an inhibitor of PLK1 and PLK3, the results showed that GW843682X down-regulated Pam3CSK4- and LPS-induced TNF-¦Á at both the gene and protein levels. GW843682X did not impact Pam3CSK4-induced IL-1¦Â and IL-8 or LPS-induced IL-1¦Â, but it down-regulated LPS-induced IL-8 significantly. Moreover, western blot results showed that TLRs activated PLK1, and PLK1 inhibition by RNA interference down-regulated Pam3CSK4-induced TNF-¦Á production, suggesting the involvement of PLK1 in TNF-¦Á up-regulation. In addition, GW843682X treatment for 12 to 24 h induced cell death and down-regulated MyD88, but neither of these roles contributed to the down-regulation of TNF-¦Á, as TNF-¦Á gene expression was up-regulated at 1 h. Furthermore, GW843682X inhibited Pam3CSK4-induced activation of ERK and NF-¦ÊB, which contributed to Pam3CSK4-induced up-regulation of TNF-¦Á. GW843682X also inhibited LPS-induced activation of ERK, p38 and NF-¦ÊB, which contributed to LPS-induced up-regulation of TNF-¦Á. Taken together, these results suggested that PLK1 is involved in TLR2- and TLR4-induced inflammation, and GW843682X may be valuable for the regulation of the inflammatory response.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0078832