title: Muramyl dipeptide potentiates staphylococcal lipoteichoic acid induction of cyclooxygenase-2 expression in macrophages.
abstract: Gram-positive bacteria contain lipoteichoic acid (LTA) and peptidoglycan (PGN) layers, both of which are considered as major virulence factors associated with inflammation. Cyclooxygenase-2 (COX-2) plays an important role in the inflammation by generating prostaglandins at infections. Since LTA and PGN are thought to cooperate in the establishment of inflammation, we examined the ability of staphylococcal LTA (Sa.LTA) to induce COX-2 expression in the presence of muramyl dipeptide (MDP), which is the minimal structural unit of PGN required for inflammation, in macrophages. While MDP failed to induce COX-2 expression, Sa.LTA alone was sufficient to induce COX-2 production. Treatment with MDP enhanced Sa.LTA-induced COX-2 and prostaglandin E2 production. The cooperative effect between Sa.LTA and MDP was not observed in COX-2 expression by macrophages derived from Toll-like receptor 2 (TLR2)- or nucleotide-binding oligomerization domain 2 (NOD2)-deficient mice. In addition, MDP enhanced Sa.LTA-induced activation of the transcription factors NF-κB and CRE, which are known to modulate COX-2 gene transcription. Conclusively, these results suggest that MDP and Sa.LTA cooperatively induce inflammatory response by overproducing COX-2 through NOD2 and TLR2.
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea.
authors.forename: Ki Bum
authors.initials: KB
authors.lastname: Ahn
authors.affiliation: Division of High-risk Pathogen Research, Center for Infectious Diseases, Korean National Institute of Health, Cheongwon-gun, Chungbuk 363-951, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Baik
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea.
authors.forename: Ok-Jin
authors.initials: OJ
authors.lastname: Park
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea.
authors.forename: Seok-Seong
authors.initials: SS
authors.lastname: Kang
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-718, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-749, Republic of Korea. Electronic address: shhan-mi@snu.ac.kr.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Han
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D054884:Host-Pathogen Interactions; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D018345:Mice, Knockout; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D013682:Teichoic Acids / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000276:immunology
chemical_list: D008070:Lipopolysaccharides; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D013682:Teichoic Acids; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C009900:lipoteichoic acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2
keywords: Cyclooxygenase-2; Lipoteichoic acid; Muramyl dipeptide; NOD2; Staphylococcus aureus; TLR2