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Analysis of Interleukin‐Activated Human Gingival Fibroblasts: Modulation of Chemokine Responses by Female Hormones
Author(s) -
Lapp Carol A.,
Lapp David F.
Publication year - 2005
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2005.76.5.803
Subject(s) - chemokine , immune system , hormone , interleukin 8 , ccl7 , progestin , interleukin , biology , immunology , endocrinology , medicine , inflammation , cytokine , chemokine receptor
Background: The female sex hormones are known to affect the response of numerous tissues to an immune challenge. Because such hormones normally fluctuate during puberty, pregnancy, and the menstrual cycle, more information about the hormonal modulation of such responses in the oral cavity is needed. Gingival fibroblasts (GF), major components of the oral tissues, are potentially sources for inflammatory mediators. Methods: Macroarrays specific for cytokines and related proteins were used to examine the regulation of gene expression in GF under serum‐free, resting conditions, after immune challenge with interleukin‐1β (IL‐1β), and in the presence of IL‐1β plus a progestin, ±17β‐estradiol. Additional studies used enzymelinked immunosorbent assays (ELISAs) to test for secreted chemokines after the same treatments. Results: Of the 392 genes on the macroarray, 66 were up‐ or downregulated at least 2‐fold relative to the unstimulated control in an average of six different sub‐lines. Chemokines represented the largest group (18%) of these regulated genes. Numerous genes whose expression was upregulated by IL‐1β were modulated downward by IL‐1β plus progestin, ±17β‐estradiol. Measurements of the secretion of IL‐8, a CXC chemokine, and MCP‐1, a CC chemokine, confirmed the inhibitory effect of a progestin on these genes. Conclusions: Gingival fibroblasts are active participants in the immune response in the oral cavity, and may potentially produce many chemokine signals after exposure to IL‐1β. GF can attract neutrophils, monocytes, eosinophils, and fibroblasts to the area of injury, and aid in the wound repair process. The concentration of female sex hormones, especially progestin, may significantly affect these signaling systems. J Periodontol 2005;76:803‐812 .