title: Interleukin-1 receptor-associated kinase-M in gingival epithelial cells attenuates the inflammatory response elicited by Porphyromonas gingivalis.
abstract: OBJECTIVE
  Recent studies have revealed that negative regulatory molecules, including interleukin-1 receptor-associated kinase-M (IRAK-M), control the overactivation of Toll-like receptor (TLR) signaling. The role of IRAK-M in human gingival epithelial cells (HGECs), which express TLRs, remains unclear. The present study examined the role of IRAK-M on interleukin-8 and macrophage chemoattractant protein-1 (MCP-1) expression in HGECs stimulated with Porphyromonas gingivalis and TLR ligands.
  
  
  METHODS
  Primary HGECs and an SV40 T-antigen-immortalized HGEC line (epi 4) were stimulated with live or heat-killed P. gingivalis, P. gingivalis lipopolysaccharide or the synthetic lipopeptide PAM(3)CSK(4), and subsequent expression of IRAK-M, interleukin-8 and MCP-1 was evaluated at the mRNA and protein levels. The effects of IRAK-M on interleukin-8 and MCP-1 expressions were evaluated by IRAK-M-specific RNA interference (RNAi)-based loss-of-function assay.
  
  
  RESULTS
  All tested stimulants up-regulated the expression of IRAK-M in HGECs. The P. gingivalis lipopolysaccharide or PAM(3)CSK(4) increased MCP-1 expression, whereas live P. gingivalis down-regulated the MCP-1 expression in HGECs. However, IRAK-M RNAi increased the expression of MCP-1 irrespective of up- or down-regulation mediated by the respective stimulants. Interleukin-8 gene expression, up-regulated by all tested stimulants, was further enhanced by IRAK-M RNAi. In contrast, IRAK-M RNAi had no effect on the interleukin-8 protein levels, irrespective of the stimulant, indicating that post-translational modification, not IRAK-M, controls interleukin-8 protein expression.
  
  
  CONCLUSIONS
  Interleukin-1 receptor-associated kinase-M appeared to have distinct regulatory roles on the interleukin-8 and MCP-1 produced by HGECs, further suggesting an important role for interleukin-8 in the immune response to periodontopathic bacteria.
authors.affiliation: Center for Transdisciplinary Research, Niigata University, Niigata, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: H
authors.initials: H
authors.lastname: Domon
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: K
authors.initials: K
authors.lastname: Tabeta
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology; D020868:Gene Silencing; D005881:Gingiva / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology*; D016209:Interleukin-8 / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D055666:Lipopeptides / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis; D016966:Porphyromonas gingivalis / Q000276:immunology*; D011499:Protein Processing, Post-Translational / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000032:analysis; D051193:Toll-Like Receptors / Q000819:agonists / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D008024:Ligands; D055666:Lipopeptides; D008070:Lipopolysaccharides; C508075:Pam(3)CSK(4) peptide; D034741:RNA, Small Interfering; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051193:Toll-Like Receptors; C507771:IRAK3 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases