title: Molecular and cellular mechanisms for periodontal diseases: role of Th1 and Th2 type cytokines in induction of mucosal inflammation.
abstract: An accumulation of elevated numbers of macrophages (M phi) and Ig producing cells is associated with localized and chronically inflamed gingiva of patients with adult periodontitis. When gingival lymphocytes were isolated from inflamed tissues and examined by flow cytometry, approximately 20-30% of lymphocytes were CD4+ T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4+ T cells, RNA was extracted and reverse transcriptase polymerase chain reaction (RT-PCR) was performed by using specific 5' and 3' primers for IFN-gamma and IL-2 (Th1), IL-4, IL-5, IL-6, IL-10 and IL-13, (Th2) and beta-actin (housekeeping gene). Two distinct cytokine profiles were noted based on the expression of selected Th1 and Th2 cytokines. Thus, one pattern was represented by the expression of mRNA for IFN-gamma, IL-6, IL-10 and IL-13, while the other case consisted of mRNA for IFN-gamma, IL-6, and IL-13. Except for a few cases, messages for IL-2, IL-4 and IL-5 were not detected by cytokine-specific RT-PCR. The predominant expression of Th2 cytokines (e.g. IL-6, IL-10 and IL-13) may contribute to the induction of high B cell responses in local disease sites. On the other hand, lack of IL-4 may be responsible for the accumulation of M phi in diseased periodontium. We also investigated whether a relationship exists between IL-4 receptor (IL-4R) expression and M phi persistence in the absence of exogenous IL-4. Gingival M phi, when compared with monocytes (MN)/M phi from peripheral blood mononuclear cells (PBMC), expressed high levels of IL-4R mRNA. When gingival M phi were incubated with recombinant IL-4 (rIL-4), the cell viability was dramatically reduced by apoptosis. These findings clearly show that the lack of IL-4 may contribute to the persistent occurrence of M phi at the disease site and addition of exogenous rIL-4 to gingival M phi cultures leads to cell death by apoptosis.
authors.affiliation: Department of Oral Biology, University of Alabama at Birmingham 35294, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Fujihashi
authors.forename: T
authors.initials: T
authors.lastname: Hiroi
authors.forename: J R
authors.initials: JR
authors.lastname: McGhee
authors.forename: T E
authors.initials: TE
authors.lastname: Van Dyke
authors.forename: H
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D016207:Cytokines / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D018928:Immunity, Mucosal / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D007378:Interleukins / Q000096:biosynthesis; D009000:Monocytes / Q000378:metabolism; D010510:Periodontal Diseases / Q000276:immunology*; D018123:Receptors, Interleukin / Q000378:metabolism; D019948:Receptors, Interleukin-4; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D007376:Interleukin-2; D007378:Interleukins; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007371:Interferon-gamma