IL-10 gene transfer attenuates P. gingivalis-induced inflammation

Yael Houri-Haddad, W.A. Soskolne, A. Halabi, L. Shapira

    Research output: Contribution to journalArticlepeer-review

    20 Scopus citations


    IL-10 is an anti-inflammatory cytokine secreted by stimulated Th2 lymphocytes that can downregulate inflammatory responses to bacterial challenge. We hypothesized that local delivery of IL-10 using gene-transfer will down-regulate inflammatory responses. We examined the effect of IL-10 plasmid injection on the local cytokine response. Two weeks after the implantation of chambers, either IL-10 plasmid or vector was injected into the mice. Four days later, they were challenged with an intra-chamber injection of P. gingivalis. The intra-chamber levels of IL-10, IFNγ,NFα, and IL-Iβ were evaluated after 2 and 24 hrs. The results showed that local IL-10 gene delivery elevated the levels of IL-10 at both time periods. It attenuated the levels of IFNγ (656 ± 154 to 218 ±144 pg/mL) and TNFα (23 ±2.0 to 12.5 ±2.9 ng/mL) at 2 hrs, and of IL-lβ (21.5 ± 5.7 to 12.4 ±3.0 ng/mL) at 24 hrs. The results suggest the possibility of modulating the local inflammatory response to P. gingivalis by direct IL-10 gene transfer.
    Original languageEnglish
    Pages (from-to)560-564
    Number of pages5
    JournalJournal of Dental Research
    Issue number6
    StatePublished - 2007

    Bibliographical note

    Cited By :17

    Export Date: 27 November 2022


    Correspondence Address: Houri-Hoddod, Y.; Department of Periodontology, PO Box 12272, Jerusalem 91120, Israel; email:

    Chemicals/CAS: gamma interferon, 82115-62-6; Inflammation Mediators; Interferon Type II, 82115-62-6; Interleukin-10, 130068-27-8; Interleukin-1beta; Tumor Necrosis Factor-alpha

    Funding text 1: The study was supported by a grant from the US-Israel Bi National Research Foundation.

    References: Al-Rasheed, A., Scheerens, H., Rennick, D.M., Fletcher, H.M., Tatakis, D.N., Accelerated alveolar bone loss in mice lacking interleukin 10 (2003) J Dent Res, 82, pp. 632-635; Apparailly, F., Millet, V., Noel, D., Jacquet, C., Sany, J., Jorgensen, C., Tetracycline-inducible interleukin-10 gene transfer mediated by an adeno-associated virus: Application to experimental arthritis (2002) Hum Gene Ther, 13, pp. 1179-1188; Asadullah, K., Sterry, W., Stephanek, K., Jasulitis, D., Leupold, M., Audring, H., IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: A new therapeutic approach (1998) J Clin Invest, 101, pp. 783-794; Baker, P.J., Evans, R.T., Roopenian, D.C., Oral infection with Porphyromonas gingivalis and induced alveolar bone loss in immunocompetent and severe combined immunodeficient mice (1994) Arch OralBiol, 39, pp. 1035-1040; Berg, D.J., Kuhn, R., Rajewsky, K., Muller, W., Menon, S., Davidson, N., Interleukin-10 is a central regulator of the response to LPS in murine models of endotoxic shock and the Shwartzman reaction but not endotoxin tolerance (1995) J Clin Invest, 96, pp. 2339-2347; Berg, D.J., Davidson, N., Kuhn, R., Muller, W., Menon, S., Holland, G., Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses (1996) J Clin Invest, 98, pp. 1010-1020; Bogdan, C., Vodovotz, Y., Nathan, C., Macrophage deactivation by interleukin W (1991) J Exp Med, 174, pp. 1549-1555; Chernoff, A.E., Granowitz, E.V., Shapiro, L., Vannier, E., Lonnemann, G., Angel, J.B., A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses (1995) J Immunol, 154, pp. 5492-5499; Cuzzocrea, S., Mazzon, E., Dugo, L., Serranio, I., Britti, D., De Maio, M., Absence of endogenous interleukin-10 enhances the evolution of murine type-II collagen-induced arthritis (2001) Eur Cytokine Netw, 12, pp. 568-580; Daheshia, M., Kuklin, N., Kanangat, S., Manickan, E., Rouse, B.T., Suppression of ongoing ocular inflammatory disease by topical administration of plasmid DNA encoding IL-10 (1997) J Immunol, 159, pp. 1945-1952; Fiorentino, D.F., Zlotnik, A., Mosmann, T.R., Howard, M., O'Garra, A., IL-10 inhibits cytokine production by activated macrophages (1991) J Immunol, 147, pp. 3815-3822; Frolov, I., Houri-Haddad, Y., Soskolne, A., Shapira, L., In vivo exposure to Porphyromonas gingivalis up-regulates nitric oxide but suppresses tumor necrosis factor alpha production by cultured macrophages (1998) Immunology, 93, pp. 323-328; Genco, C.A., Arko, R.J., Animal chamber models for study of hostparasite interactions (1994) Methods Enzymol, 235, pp. 120-140; Houri-Haddad, Y., Soskolne, W.A., Halabi, A., Barak, V., Shapira, L., Repeat bacterial challenge in a subcutaneous chamber model results in augmented tumour necrosis factor-alpha and interferongamma response, and suppression of interleukin-10 (2000) Immunology, 99, pp. 215-220; Itoh, K., Inoue, T., Ito, K., Hirohata, S., The interplay of interleukin10 (IL-10) and interleukin-2 (IL-2) in humoral immune responses: IL-10 synergizes with IL-2 to enhance responses of human B lymphocytes in a mechanism which is different from upregulation of CD25 expression (1994) Cell Immunol, 157, pp. 478-488; Kesavalu, L., Ebersole, J.L., Machen, R.L., Holt, S.C., Porphyromonas gingivalis virulence in mice: Induction of immunity to bacterial components (1992) Infect Immun, 60, pp. 1455-1464; Mosmann, T.R., Coffman, R.L., Thl and Th2 cells: Different patterns of lymphokine secretion lead to different functional properties (1989) Annu Rev Immunol, 7, pp. 145-173; Owens, J.M., Gallagher, A.C., Chambers, T.J., IL-10 modulates formation of osteoclasts in murine hemopoietic cultures (1996) J Immunol, 157, pp. 936-940; Pihlstrom, B.L., Michalowicz, B.S., Johnson, N.W., Periodontal diseases (2005) Lancet, 366, pp. 1809-1820; Puliti, M., Von Hunolstein, C., Verwaerde, C., Bistoni, F., Orefici, G., Tissi, L., Regulatory role of interleukin-10 in experimental group B streptococcal arthritis (2002) Infect Immun, 70, pp. 2862-2868; Ralph, P., Nakoinz, I., Sampson-Johannes, A., Fong, S., Lowe, D., Min, H.Y., IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor (1992) J Immunol, 148, p. 808814; Rogy, M.A., Auffenberg, T., Espat, N.J., Philip, R., Remick, D., Wollenberg, G.K., Human tumor necrosis factor receptor (p55) and interleukin 10 gene transfer in the mouse reduces mortality to lethal endotoxemia and also attenuates local inflammatory responses (1995) J Exp Med, 181, pp. 2289-2293; Socransky, S.S., Haffajee, A.D., The bacterial etiology of destructive periodontal disease: Current concepts (1992) J Periodontol 63(4Suppl), pp. 322-331; Taubman, M.A., Valverde, P., Han, X., Kawai, T., Immune response: The key to bone resorption in periodontal disease (2005) J Periodontol 76(11Suppl), pp. 2033-2041; Van Dyke, T.E., Lester, M.A., Shapira, L., The role of host response in periodontal disease progression: Implications for future treatment strategies (1993) J Periodontol, 64 (8 SUPPL.), pp. 792-806; Walmsley, M., Katsikis, P.D., Abney, E., Parry, S., Williams, R.O., Maini, R.N., Interleukin-10 inhibition of the progression of the established collagen-induced arthritis (1996) Arthritis Rheum, 39, pp. 495-503


    • Gene transfer
    • Inflammation
    • Porphyromonas gingivalis
    • autacoid
    • gamma interferon
    • interleukin 10
    • interleukin 1beta
    • tumor necrosis factor alpha
    • animal
    • article
    • Bagg albino mouse
    • chemistry
    • diffusion chamber
    • down regulation
    • exudate
    • female
    • gene transfer
    • gene vector
    • genetics
    • immunology
    • intramuscular drug administration
    • mouse
    • time
    • Animals
    • Diffusion Chambers, Culture
    • Down-Regulation
    • Exudates and Transudates
    • Female
    • Gene Transfer Techniques
    • Genetic Vectors
    • Inflammation Mediators
    • Injections, Intramuscular
    • Interferon Type II
    • Interleukin-10
    • Interleukin-1beta
    • Mice
    • Mice, Inbred BALB C
    • Time Factors
    • Tumor Necrosis Factor-alpha


    Dive into the research topics of 'IL-10 gene transfer attenuates P. gingivalis-induced inflammation'. Together they form a unique fingerprint.

    Cite this