| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Microbiology and
Oral Biology, University of Alabama, Birmingham, AL 35294;
Department of Oral Biology, State University of New York, Buffalo, NY 14214; and
Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 20814
Stimulation of the APC by Porphyromonas gingivalis LPS has been shown to result in the production of certain pro- and anti-inflammatory cytokines. However, the signaling pathways that regulate these processes are currently unknown. In the present study, the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in regulating P. gingivalis LPS-induced production of IL-10, IL-12 p40, and IL-12 p70 by human monocytes was investigated. P. gingivalis LPS selectively activates the PI3K-Akt pathway via Toll-like receptor 2, and inhibition of this pathway results in an abrogation of extracellular signal-regulated kinase 1/2 phosphorylation, whereas the activation of p38 and c-Jun N-terminal kinase 1/2 kinases were unaffected. Analysis of cytokine production following stimulation of monocytes with P. gingivalis LPS revealed that inhibition of the PI3K pathway differentially regulated IL-10 and IL-12 synthesis. IL-10 production was suppressed, whereas IL-12 levels were enhanced. Inhibition of P. gingivalis LPS-mediated activation of the PI3K-Akt pathway resulted in a pronounced augmentation of NF-
B p65 that was independent of IB-
degradation. Furthermore, the ability of the PI3K-Akt pathway to modulate IL-10 and IL-12 production appears to be mediated by the selective suppression of extracellular signal-regulated kinase 1/2 activity, as the MEK1 inhibitor PD98059 closely mimicked the effects of wortmannin and LY294002 to differentially regulate IL-10 and IL-12 production by P. gingivalis LPS-stimulated monocytes. These studies provide new insight into how engagement of the PI3K-Akt pathway by P. gingivalis LPS affects the induction of key immunoregulatory cytokines that control both qualitative and quantitative aspects of innate and adaptive immunity.
This article has been cited by other articles:
|
|
 |
|
  C. Chandras, Y. Koutmani, E. Kokkotou, C. Pothoulakis, and K. P. Karalis Activation of Phosphatidylinositol 3-Kinase/Protein Kinase B by Corticotropin-Releasing Factor in Human Monocytes Endocrinology, October 1, 2009; 150(10): 4606 - 4614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Garcia, H. Wang, M. R. Benakanakere, E. Barrett, D. F. Kinane, and M. Martin c-Jun Controls the Ability of IL-12 to Induce IL-10 Production from Human Memory CD4+ T Cells J. Immunol., October 1, 2009; 183(7): 4475 - 4482. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. P. Chan, B. K. W. Cheung, J. C. B. Li, L. L. Y. Chan, and A. S. Y. Lau A role for glycogen synthase kinase-3 in antagonizing mycobacterial immune evasion by negatively regulating IL-10 induction J. Leukoc. Biol., August 1, 2009; 86(2): 283 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nasso, G. Fedele, F. Spensieri, R. Palazzo, P. Costantino, R. Rappuoli, and C. M. Ausiello Genetically Detoxified Pertussis Toxin Induces Th1/Th17 Immune Response through MAPKs and IL-10-Dependent Mechanisms J. Immunol., August 1, 2009; 183(3): 1892 - 1899. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. W. Laird, S. H. Rhee, D. J. Perkins, A. E. Medvedev, W. Piao, M. J. Fenton, and S. N. Vogel TLR4/MyD88/PI3K interactions regulate TLR4 signaling J. Leukoc. Biol., June 1, 2009; 85(6): 966 - 977. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Janes and D. A. Fruman Immune Regulation by Rapamycin: Moving Beyond T Cells Sci. Signal., April 21, 2009; 2(67): pe25 - pe25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sun, R. D. Ramnath, R. Tamizhselvi, and M. Bhatia Role of protein kinase C and phosphoinositide 3-kinase-Akt in substance P-induced proinflammatory pathways in mouse macrophages FASEB J, April 1, 2009; 23(4): 997 - 1010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Rehani, H. Wang, C. A. Garcia, D. F. Kinane, and M. Martin Toll-Like Receptor-Mediated Production of IL-1Ra Is Negatively Regulated by GSK3 via the MAPK ERK1/2 J. Immunol., January 1, 2009; 182(1): 547 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Karumuthil-Melethil, N. Perez, R. Li, and C. Vasu Induction of Innate Immune Response through TLR2 and Dectin 1 Prevents Type 1 Diabetes J. Immunol., December 15, 2008; 181(12): 8323 - 8334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Garcia, M. R. Benakanakere, P. Alard, M. M. Kosiewicz, D. F. Kinane, and M. Martin Antigenic Experience Dictates Functional Role of Glycogen Synthase Kinase-3 in Human CD4+ T Cell Responses J. Immunol., December 15, 2008; 181(12): 8363 - 8371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quante and T. C. Wang Inflammation and Stem Cells in Gastrointestinal Carcinogenesis Physiology, December 1, 2008; 23(6): 350 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Weichhart and M D Saemann The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications Ann Rheum Dis, December 1, 2008; 67(Suppl_3): iii70 - iii74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Tachado, X. Li, K. Swan, N. Patel, and H. Koziel Constitutive Activation of Phosphatidylinositol 3-Kinase Signaling Pathway Down-regulates TLR4-mediated Tumor Necrosis Factor-{alpha} Release in Alveolar Macrophages from Asymptomatic HIV-positive Persons in Vitro J. Biol. Chem., November 28, 2008; 283(48): 33191 - 33198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, C. A. Garcia, K. Rehani, C. Cekic, P. Alard, D. F. Kinane, T. Mitchell, and M. Martin IFN-{beta} Production by TLR4-Stimulated Innate Immune Cells Is Negatively Regulated by GSK3-{beta} J. Immunol., November 15, 2008; 181(10): 6797 - 6802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohtani, S. Nagai, S. Kondo, S. Mizuno, K. Nakamura, M. Tanabe, T. Takeuchi, S. Matsuda, and S. Koyasu Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells Blood, August 1, 2008; 112(3): 635 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Luyendyk, G. A. Schabbauer, M. Tencati, T. Holscher, R. Pawlinski, and N. Mackman Genetic Analysis of the Role of the PI3K-Akt Pathway in Lipopolysaccharide-Induced Cytokine and Tissue Factor Gene Expression in Monocytes/Macrophages J. Immunol., March 15, 2008; 180(6): 4218 - 4226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Domon, T. Honda, T. Oda, H. Yoshie, and K. Yamazaki Early and preferential induction of IL-1 receptor-associated kinase-M in THP-1 cells by LPS derived from Porphyromonas gingivalis J. Leukoc. Biol., March 1, 2008; 83(3): 672 - 679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Dower, D. K. Ellis, K. Saraf, S. A. Jelinsky, and L.-L. Lin Innate Immune Responses to TREM-1 Activation: Overlap, Divergence, and Positive and Negative Cross-Talk with Bacterial Lipopolysaccharide J. Immunol., March 1, 2008; 180(5): 3520 - 3534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Lambert and O. M. Martinez Latent Membrane Protein 1 of EBV Activates Phosphatidylinositol 3-Kinase to Induce Production of IL-10 J. Immunol., December 15, 2007; 179(12): 8225 - 8234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Polumuri, V. Y. Toshchakov, and S. N. Vogel Role of Phosphatidylinositol-3 Kinase in Transcriptional Regulation of TLR-Induced IL-12 and IL-10 by Fc{gamma} Receptor Ligation in Murine Macrophages J. Immunol., July 1, 2007; 179(1): 236 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Agrawal, S. Agrawal, J.-N. Cao, H. Su, K. Osann, and S. Gupta Altered Innate Immune Functioning of Dendritic Cells in Elderly Humans: A Role of Phosphoinositide 3-Kinase-Signaling Pathway J. Immunol., June 1, 2007; 178(11): 6912 - 6922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Ma, S. Mishra, K. Gee, J. P. Mishra, D. Nandan, N. E. Reiner, J. B. Angel, and A. Kumar Cyclosporin A and FK506 Inhibit IL-12p40 Production through the Calmodulin/Calmodulin-dependent Protein Kinase-activated Phosphoinositide 3-Kinase in Lipopolysaccharide-stimulated Human Monocytic Cells J. Biol. Chem., May 4, 2007; 282(18): 13351 - 13362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pompei, S. Jang, B. Zamlynny, S. Ravikumar, A. McBride, S. P. Hickman, and P. Salgame Disparity in IL-12 Release in Dendritic Cells and Macrophages in Response to Mycobacterium tuberculosis Is Due to Use of Distinct TLRs J. Immunol., April 15, 2007; 178(8): 5192 - 5199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Into, Y. Kanno, J.-i. Dohkan, M. Nakashima, M. Inomata, K.-i. Shibata, C. J. Lowenstein, and K. Matsushita Pathogen Recognition by Toll-like Receptor 2 Activates Weibel-Palade Body Exocytosis in Human Aortic Endothelial Cells J. Biol. Chem., March 16, 2007; 282(11): 8134 - 8141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sen, M. A. Wallet, Z. Yi, Y. Huang, M. Henderson, C. E. Mathews, H. S. Earp, G. Matsushima, A. S. Baldwin Jr, and R. M. Tisch Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-{kappa}B activation in dendritic cells Blood, January 15, 2007; 109(2): 653 - 660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Molnarfi, L. Gruaz, J.-M. Dayer, and D. Burger Opposite Regulation of IL-1beta and Secreted IL-1 Receptor Antagonist Production by Phosphatidylinositide-3 Kinases in Human Monocytes Activated by Lipopolysaccharides or Contact with T Cells J. Immunol., January 1, 2007; 178(1): 446 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. He, L. W. Shepard, J. Chen, Z. K. Pan, and R. D. Ye Serum Amyloid A Is an Endogenous Ligand That Differentially Induces IL-12 and IL-23 J. Immunol., September 15, 2006; 177(6): 4072 - 4079. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.W. Cutler and R. Jotwani Dendritic Cells at the Oral Mucosal Interface Journal of Dental Research, August 1, 2006; 85(8): 678 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Y. Lee, M.-K. Kim, K. S. Park, E. H. Shin, S. H. Jo, S. D. Kim, E. J. Jo, Y.-N. Lee, C. Lee, S.-H. Baek, et al. Serum Amyloid A Induces Contrary Immune Responses via Formyl Peptide Receptor-Like 1 in Human Monocytes Mol. Pharmacol., July 1, 2006; 70(1): 241 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Kim and E. Y. Denkers Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis J. Cell Sci., May 15, 2006; 119(10): 2119 - 2126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Katz, P. Zhang, M. Martin, S. N. Vogel, and S. M. Michalek Toll-Like Receptor 2 Is Required for Inflammatory Responses to Francisella tularensis LVS. Infect. Immun., May 1, 2006; 74(5): 2809 - 2816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Zhou and S. Amar Identification of Proteins Differentially Expressed in Human Monocytes Exposed to Porphyromonas gingivalis and Its Purified Components by High-Throughput Immunoblotting Infect. Immun., February 1, 2006; 74(2): 1204 - 1214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Tomczak, M. Gadjeva, Y. Y. Wang, K. Brown, I. Maroulakou, P. N. Tsichlis, S. E. Erdman, J. G. Fox, and B. H. Horwitz Defective Activation of ERK in Macrophages Lacking the p50/p105 Subunit of NF-{kappa}B Is Responsible for Elevated Expression of IL-12 p40 Observed after Challenge with Helicobacter hepaticus J. Immunol., January 15, 2006; 176(2): 1244 - 1251. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. N. Waggoner, M. W. Cruise, R. Kassel, and Y. S. Hahn gC1q Receptor Ligation Selectively Down-Regulates Human IL-12 Production through Activation of the Phosphoinositide 3-Kinase Pathway J. Immunol., October 1, 2005; 175(7): 4706 - 4714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Kang, H.-Y. Lee, M.-K. Kim, K. S. Park, Y. M. Park, J.-Y. Kwak, and Y.-S. Bae The Synthetic Peptide Trp-Lys-Tyr-Met-Val-D-Met Inhibits Human Monocyte-Derived Dendritic Cell Maturation via Formyl Peptide Receptor and Formyl Peptide Receptor-Like 2 J. Immunol., July 15, 2005; 175(2): 685 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Zhang, M. Martin, S. M. Michalek, and J. Katz Role of Mitogen-Activated Protein Kinases and NF-{kappa}B in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines by Porphyromonas gingivalis Hemagglutinin B Infect. Immun., July 1, 2005; 73(7): 3990 - 3998. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Strassheim, J.-Y. Kim, J.-S. Park, S. Mitra, and E. Abraham Involvement of SHIP in TLR2-Induced Neutrophil Activation and Acute Lung Injury J. Immunol., June 15, 2005; 174(12): 8064 - 8071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Merck, B. de Saint-Vis, M. Scuiller, C. Gaillard, C. Caux, G. Trinchieri, and E. E. M. Bates Fc receptor {gamma}-chain activation via hOSCAR induces survival and maturation of dendritic cells and modulates Toll-like receptor responses Blood, May 1, 2005; 105(9): 3623 - 3632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Muthukuru, R. Jotwani, and C. W. Cutler Oral Mucosal Endotoxin Tolerance Induction in Chronic Periodontitis Infect. Immun., February 1, 2005; 73(2): 687 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. S. Park, H. Y. Jung, E. Y. Park, J. Kim, W. J. Lee, and Y. S. Bae Cutting Edge: Direct Interaction of TLR4 with NAD(P)H Oxidase 4 Isozyme Is Essential for Lipopolysaccharide-Induced Production of Reactive Oxygen Species and Activation of NF-{kappa}B J. Immunol., September 15, 2004; 173(6): 3589 - 3593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhattacharyya, P. Sen, M. Wallet, B. Long, A. S. Baldwin Jr, and R. Tisch Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of I{kappa}B kinase activity Blood, August 15, 2004; 104(4): 1100 - 1109. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Spaner Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells J. Leukoc. Biol., August 1, 2004; 76(2): 338 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. R. Gockel, A. Lugering, J. Heidemann, M. Schmidt, W. Domschke, T. Kucharzik, and N. Lugering Thalidomide Induces Apoptosis in Human Monocytes by Using a Cytochrome c-Dependent Pathway J. Immunol., April 15, 2004; 172(8): 5103 - 5109. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
