| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Defensin-2 in Gingival Epithelial Cells: The Involvement of Mitogen-Activated Protein Kinase Pathways, But Not the NF-
B Transcription Factor Family1
,
,
Departments of
*
Oral Biology and
Periodontics, School of Dentistry, and Departments of
Biochemistry and
Medicine/Dermatology, School of Medicine, University of Washington, Seattle, WA 98195
Stratified epithelia of the oral cavity are continually exposed to
bacterial challenge that is initially resisted by neutrophils and
epithelial factors, including antimicrobial peptides of the
-defensin family. Previous work has shown that multiple signaling
pathways are involved in human -defensin (hBD)-2 mRNA regulation in
human gingival epithelial cells stimulated with a periodontal
bacterium, Fusobacterium nucleatum, and other
stimulants. The goal of this study was to further characterize these
pathways. The role of NF-
B in hBD-2 regulation was investigated
initially due to its importance in inflammation and infection. Nuclear
translocation of p65 and NF-B activation was seen in human gingival
epithelial cells stimulated with F. nucleatum cell wall
extract, indicating possible involvement of NF-B in hBD-2
regulation. However, hBD-2 induction by F. nucleatum was
not blocked by pretreatment with two NF-B inhibitors, pyrrolidine
dithiocarbamate and the proteasome inhibitor, MG132. To
investigate alternative modes of hBD-2 regulation, we explored
involvement of mitogen-activated protein kinase pathways. F.
nucleatum activated p38 and c-Jun
NH2-terminal kinase (JNK) pathways, whereas it had
little effect on p44/42. Furthermore, inhibition of p38 and JNK
partially blocked hBD-2 mRNA induction by F. nucleatum,
and the combination of two inhibitors completely blocked expression.
Our results suggest that NF-B is neither essential nor sufficient
for hBD-2 induction, and that hBD-2 regulation by F.
nucleatum is via p38 and JNK, while phorbol ester induces hBD-2
via the p44/42 extracellular signal-regulated kinase pathway. Studies
of hBD-2 regulation provide insight into how its expression may be
enhanced to control infection locally within the mucosa and thereby
reduce microbial invasion into the underlying
tissue.
This article has been cited by other articles:
|
|
 |
|
  S. Ji, J. E. Shin, Y. S. Kim, J.-E. Oh, B.-M. Min, and Y. Choi Toll-Like Receptor 2 and NALP2 Mediate Induction of Human Beta-Defensins by Fusobacterium nucleatum in Gingival Epithelial Cells Infect. Immun., March 1, 2009; 77(3): 1044 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Diamond, N. Beckloff, and L.K. Ryan Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences Journal of Dental Research, October 1, 2008; 87(10): 915 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Cosseau, D. A. Devine, E. Dullaghan, J. L. Gardy, A. Chikatamarla, S. Gellatly, L. L. Yu, J. Pistolic, R. Falsafi, J. Tagg, et al. The Commensal Streptococcus salivarius K12 Downregulates the Innate Immune Responses of Human Epithelial Cells and Promotes Host-Microbe Homeostasis Infect. Immun., September 1, 2008; 76(9): 4163 - 4175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-Y. Kao, C. Kim, F. Huang, and R. Wu Requirements for Two Proximal NF-{kappa}B Binding Sites and I{kappa}B-{zeta} in IL-17A-induced Human {beta}-Defensin 2 Expression by Conducting Airway Epithelium J. Biol. Chem., May 30, 2008; 283(22): 15309 - 15318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Handfield, H.V. Baker, and R.J. Lamont Beyond Good and Evil in the Oral Cavity: Insights into Host-Microbe Relationships Derived from Transcriptional Profiling of Gingival Cells Journal of Dental Research, March 1, 2008; 87(3): 203 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Krisanaprakornkit, P. Chotjumlong, P. Kongtawelert, and V. Reutrakul Involvement of phospholipase D in regulating expression of anti-microbial peptide human -defensin-2 Int. Immunol., January 1, 2008; 20(1): 21 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Dommisch, W. O. Chung, M. G. Rohani, D. Williams, M. Rangarajan, M. A. Curtis, and B. A. Dale Protease-Activated Receptor 2 Mediates Human Beta-Defensin 2 and CC Chemokine Ligand 20 mRNA Expression in Response to Proteases Secreted by Porphyromonas gingivalis Infect. Immun., September 1, 2007; 75(9): 4326 - 4333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yin and B. A. Dale Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human {beta}-defensin-2 J. Med. Microbiol., July 1, 2007; 56(7): 976 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hasegawa, J. J. Mans, S. Mao, M. C. Lopez, H. V. Baker, M. Handfield, and R. J. Lamont Gingival Epithelial Cell Transcriptional Responses to Commensal and Opportunistic Oral Microbial Species Infect. Immun., May 1, 2007; 75(5): 2540 - 2547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Linde, D. Mosier, F. Blecha, and T. Melgarejo Innate immunity and inflammation - New frontiers in comparative cardiovascular pathology Cardiovasc Res, January 1, 2007; 73(1): 26 - 36. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ouhara, H. Komatsuzawa, H. Shiba, Y. Uchida, T. Kawai, K. Sayama, K. Hashimoto, M. A. Taubman, H. Kurihara, and M. Sugai Actinobacillus actinomycetemcomitans Outer Membrane Protein 100 Triggers Innate Immunity and Production of {beta}-Defensin and the 18-Kilodalton Cationic Antimicrobial Protein through the Fibronectin-Integrin Pathway in Human Gingival Epithelial Cells Infect. Immun., September 1, 2006; 74(9): 5211 - 5220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. McNamara, M. Gallup, A. Sucher, I. Maltseva, D. McKemy, and C. Basbaum AsialoGM1 and TLR5 Cooperate in Flagellin-Induced Nucleotide Signaling to Activate Erk1/2 Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Andrian, D. Grenier, and M. Rouabhia Porphyromonas gingivalis-Epithelial Cell Interactions in Periodontitis Journal of Dental Research, May 1, 2006; 85(5): 392 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Voss, J. Wehkamp, K. Wehkamp, E. F. Stange, J. M. Schroder, and J. Harder NOD2/CARD15 Mediates Induction of the Antimicrobial Peptide Human Beta-defensin-2 J. Biol. Chem., January 27, 2006; 281(4): 2005 - 2011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, J.-P. Louboutin, D. J. Weiner, J. B. Goldberg, and J. M. Wilson Human Airway Epithelial Cells Sense Pseudomonas aeruginosa Infection via Recognition of Flagellin by Toll-Like Receptor 5 Infect. Immun., November 1, 2005; 73(11): 7151 - 7160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ishizawa, T. Suzuki, M. Yamaya, Y. X. Jia, S. Kobayashi, S. Ida, H. Kubo, K. Sekizawa, and H. Sasaki Erythromycin increases bactericidal activity of surface liquid in human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L565 - L573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V.-J. Uitto, D. Baillie, Q. Wu, R. Gendron, D. Grenier, E. E. Putnins, A. Kanervo, and J. D. Firth Fusobacterium nucleatum Increases Collagenase 3 Production and Migration of Epithelial Cells Infect. Immun., February 1, 2005; 73(2): 1171 - 1179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. O. Chung, S. R. Hansen, D. Rao, and B. A. Dale Protease-Activated Receptor Signaling Increases Epithelial Antimicrobial Peptide Expression J. Immunol., October 15, 2004; 173(8): 5165 - 5170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wehkamp, J. Harder, K. Wehkamp, B. W.-v. Meissner, M. Schlee, C. Enders, U. Sonnenborn, S. Nuding, S. Bengmark, K. Fellermann, et al. NF-{kappa}B- and AP-1-Mediated Induction of Human Beta Defensin-2 in Intestinal Epithelial Cells by Escherichia coli Nissle 1917: a Novel Effect of a Probiotic Bacterium Infect. Immun., October 1, 2004; 72(10): 5750 - 5758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-Y. Kao, Y. Chen, P. Thai, S. Wachi, F. Huang, C. Kim, R. W. Harper, and R. Wu IL-17 Markedly Up-Regulates {beta}-Defensin-2 Expression in Human Airway Epithelium via JAK and NF-{kappa}B Signaling Pathways J. Immunol., September 1, 2004; 173(5): 3482 - 3491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-i. Ogushi, A. Wada, T. Niidome, T. Okuda, R. Llanes, M. Nakayama, Y. Nishi, H. Kurazono, K. D. Smith, A. Aderem, et al. Gangliosides Act as Co-receptors for Salmonella enteritidis FliC and Promote FliC Induction of Human {beta}-Defensin-2 Expression in Caco-2 Cells J. Biol. Chem., March 26, 2004; 279(13): 12213 - 12219. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Joly, C. Maze, P. B. McCray Jr., and J. M. Guthmiller Human {beta}-Defensins 2 and 3 Demonstrate Strain-Selective Activity against Oral Microorganisms J. Clin. Microbiol., March 1, 2004; 42(3): 1024 - 1029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bals and P.S. Hiemstra Innate immunity in the lung: how epithelial cells fight against respiratory pathogens Eur. Respir. J., February 1, 2004; 23(2): 327 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. O. Chung and B. A. Dale Innate Immune Response of Oral and Foreskin Keratinocytes: Utilization of Different Signaling Pathways by Various Bacterial Species Infect. Immun., January 1, 2004; 72(1): 352 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Dale Fascination with Epithelia: Architecture, Proteins, and Functions Journal of Dental Research, November 1, 2003; 82(11): 866 - 869. [Full Text] [PDF]
|
|
|
|
|
|
S. Krisanaprakornkit, D. Jotikasthira, and B.A. Dale Intracellular Calcium in Signaling Human {beta}-Defensin-2 Expression in Oral Epithelial Cells Journal of Dental Research, November 1, 2003; 82(11): 877 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. McDermott, R. L. Redfern, B. Zhang, Y. Pei, L. Huang, and R. J. Proske Defensin Expression by the Cornea: Multiple Signalling Pathways Mediate IL-1{beta} Stimulation of hBD-2 Expression by Human Corneal Epithelial Cells Invest. Ophthalmol. Vis. Sci., May 1, 2003; 44(5): 1859 - 1865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tsutsumi-Ishii and I. Nagaoka Modulation of Human {beta}-Defensin-2 Transcription in Pulmonary Epithelial Cells by Lipopolysaccharide-Stimulated Mononuclear Phagocytes Via Proinflammatory Cytokine Production J. Immunol., April 15, 2003; 170(8): 4226 - 4236. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
