Differential regulation of cytokine genes in gingival epithelial cells challenged by Fusobacterium nucleatum and Porphyromonas gingivalis.
IL-8 mRNA in human gingival epithelial cells (HGECs) is up-regulated by Fusobacterium nucleatum, and up-/down-regulated by Porphyromonas gingivalis in a complex interaction in the early stages (< or = 4 h) after infection. The mechanisms involved in this regulation in response to F. nucleatum and/or P. gingivalis infection, and identification of co-regulated cytokine genes, are the focus of this investigation. Heat, formalin or protease treatment of F. nucleatum cells attenuated the IL-8 mRNA up-regulation. NF-kappaB, mitogen-activated protein kinase (MAPK) p38 and MAPK kinase/extracellular signal-regulated kinase (MEK/ERK) pathways were involved in IL-8 mRNA induction by F. nucleatum. Pretreatment of P. gingivalis with heat, formalin or protease enhanced IL-8 mRNA induction. NF-kappaB, MARK p38, and MEK/ERK pathways were also involved in this induction. In contrast, down-regulation of IL-8 mRNA by P. gingivalis involved MEK/ERK, but not NF-kappaB or MAPK p38 pathways. cDNA arrays analysis revealed that mRNA down-regulation by P. gingivalis is a specific reaction that only a number of genes, e.g. IL-1beta, IL-8, macrophage inflammatory protein-2alpha, and migration inhibitory factor-related protein-14, are affected based on examination of 278 cytokine/receptor genes. These data indicate that F. nucleatum and P. gingivalis trigger specific and differential gene regulation pathways in HGECs.
Huang
George T-J
GT
Division of Associated Clinical Specialties, Section of Endodontics, 23-087 CHS, 10833 Le Conte Ave., UCLA School of Dentistry, Los Angeles, CA 90095-1668, USA. gtjhuang@ucla.edu
Zhang
Hi-Bo
HB
Dang
Hoa N
HN
Haake
Susan Kinder
SK
D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology; D016967:Fusobacterium nucleatum / Q000472:pathogenicity*; D005786:Gene Expression Regulation; D005881:Gingiva / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; D016209:Interleukin-8; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger