Polo-like kinase 1 (PLK1) is involved in toll-like receptor (TLR)-mediated TNF-α production in monocytic THP-1 cells.

Abstract

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-α at both the gene and protein levels. GW843682X did not impact Pam3CSK4-induced IL-1β and IL-8 or LPS-induced IL-1β, 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-α production, suggesting the involvement of PLK1 in TNF-α 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-α, as TNF-α gene expression was up-regulated at 1 h. Furthermore, GW843682X inhibited Pam3CSK4-induced activation of ERK and NF-κB, which contributed to Pam3CSK4-induced up-regulation of TNF-α. GW843682X also inhibited LPS-induced activation of ERK, p38 and NF-κB, which contributed to LPS-induced up-regulation of TNF-α. 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.

• Authors: Jinyue Hu, Guihua Wang, Xueting Liu, Lina Zhou, Manli Jiang, Li Yang
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e78832 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24205328 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-((2-(trifluoromethyl)benzyl)oxy)thiophene-2-carboxamide
• Benzimidazoles
• Cell Cycle Proteins
• Lipopeptides
• Lipopolysaccharides
• Myeloid Differentiation Factor 88
• NF-kappa B
• Pam(3)CSK(4) peptide
• Proto-Oncogene Proteins
• Thiophenes
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha
• Protein Serine-Threonine Kinases
• polo-like kinase 1

Topics

• Animals
• Apoptosis (drug effects)
• Benzimidazoles (pharmacology)
• Cell Cycle Proteins (deficiency, genetics, metabolism)
• Cell Line
• Down-Regulation (genetics)
• Female
• Gene Expression Regulation, Enzymologic (drug effects)
• Inflammation (metabolism)
• Lipopeptides (pharmacology)
• Lipopolysaccharides (pharmacology)
• MAP Kinase Signaling System (drug effects)
• Mice
• Monocytes (cytology, metabolism)
• Myeloid Differentiation Factor 88 (genetics)
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Protein Serine-Threonine Kinases (deficiency, genetics, metabolism)
• Proto-Oncogene Proteins (deficiency, genetics, metabolism)
• RNA Interference
• Thiophenes (pharmacology)
• Toll-Like Receptors (metabolism)
• Tumor Necrosis Factor-alpha (biosynthesis)