Expression of IL-2 receptor beta and gamma chains by human gingival fibroblasts and up-regulation of adhesion to neutrophils in response to IL-2.
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) alpha, beta, and gamma 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-2Rbeta and IL-2Rgamma at mRNA and protein levels, but the expression of IL-2Ralpha could not be detected, as assessed by reverse transcriptase-polymerase chain reaction and flow cytometry. IL-2Rbeta, and -gamma expressed on HGF were functionally active, as addition of neutralizing anti-IL-2Rbeta and -gamma 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-2Rgamma 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-2Rbetagamma, 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.
Ozawa
Akiko
A
Department of Microbiology and Immunology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Tada
Hiroyuki
H
Tamai
Riyoko
R
Uehara
Akiko
A
Watanabe
Kouichi
K
Yamaguchi
Takahiro
T
Shimauchi
Hidetoshi
H
Takada
Haruhiko
H
Sugawara
Shunji
S
D000328:Adult; D015704:CD4 Antigens / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D005881:Gingiva / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D053616:Janus Kinase 3; D008070:Lipopolysaccharides / Q000494:pharmacology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D010518:Periodontitis / Q000378:metabolism; D010766:Phosphorylation; D020033:Protein Isoforms; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D015704:CD4 Antigens; D017931:DNA Primers; D019409:Interleukin-15; D007376:Interleukin-2; D008070:Lipopolysaccharides; D020033:Protein Isoforms; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3