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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Cell Line, Cells, Cultured, Chemokine CCL2, Down-Regulation, Epithelial Cells, Gene Silencing, Gingiva, Humans, Inositol Polyphosphate 5-Phosphatases, Interleukin-1 Receptor-Associated Kinases, Interleukin-8, Ligands, Lipopeptides, Lipopolysaccharides, Phosphoric Monoester Hydrolases, Porphyromonas gingivalis, Protein Processing, Post-Translational, RNA Interference, RNA, Small Interfering, Signal Transduction, Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling Proteins, Toll-Like Receptors, Up-Regulation.
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Does interleukin-1 receptor-associated kinase-M in gingival epithelial cells attenuate the inflammatory response elicited by Porphyromonas gingivalis? Context: 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. 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. 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.
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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. Final Decision: yes