Expression of IL-2 receptor β and γ chains by human gingival fibroblasts and up-regulation of adhesion to neutrophils in response to IL-2

Abstract

To investigate the role of human gingival fibroblasts (HGF), the major constituents of gingival tissue in periodontal inflammatory disease, the expression of interleukin‐2 receptor (IL‐2R) α, β, and γ chains was examined. Immunohistochemistry showed a pronounced accumulation of CD8⁺ T cells in the inflamed lamina propria of gingival tissue from patients with adult periodontitis. HGF express IL‐2Rβ and IL‐2Rγ at mRNA and protein levels, but the expression of IL‐2Rα could not be detected, as assessed by reverse transcriptase‐polymerase chain reaction and flow cytometry. IL‐2Rβ, and ‐γ expressed on HGF were functionally active, as addition of neutralizing anti‐IL‐2Rβ and ‐γ antibodies caused inhibition of the IL‐2‐induced production of monocyte chemoattractant protein‐1 (MCP‐1), and addition of IL‐2 induced phosphorylation of Janus tyrosine kinase 3, which is critical in signaling through IL‐2Rγ in HGF. The IL‐2‐induced MCP‐1 production was significantly inhibited by pretreatment with neutralizing antibody to IL‐15. Addition of IL‐2 also induced a marked up‐regulation of the expression of intercellular adhesion molecule‐1 (ICAM‐1) on the surface of HGF, which in turn, significantly augmented the adhesion of human neutrophils, which were inhibited by an anti‐ICAM‐1 antibody. These results suggest that HGF express functional IL‐2Rβγ, respond to IL‐2 from infiltrated T cells, and actively participate in the inflammatory process in the periodontal region and that IL‐15 produced by HGF sustains IL‐2‐mediated signaling in HGF.