MMPs, IL-1, and TNF are regulated by IL-17 in periodontitis.
Periodontitis is characterized by periodontal tissue destruction. Since interleukin-17 (IL-17) has been reported to up-regulate IL-1beta and tumor necrosis factor-alpha (TNF-alpha), it was hypothesized that it is increased in periodontitis and up-regulates these cytokines and tissue-destructive matrix metalloproteinases (MMP) in local migrant and resident cells. Immunocytochemistry disclosed elevated IL-1beta, TNF-alpha, and IL-17 levels in periodontitis. These cytokines induced proMMP-1 and especially MMP-3 in gingival fibroblasts, whereas MMP-8 and MMP-9 were not induced. IL-17 was less potent as a direct MMP inducer than IL-1beta and TNF-alpha, but it induced IL-1beta and TNF-alpha production from macrophages, and IL-6 and IL-8 from gingival fibroblasts. In accordance with these findings, immunocytochemistry disclosed that MMP-1 and MMP-3 were increased in periodontitis. Gingival fibroblasts may play an important role in tissue destruction in periodontitis via cytokine-inducible MMP-1 and MMP-3 production, in which IL-17 plays a role as a key regulatory cytokine.
Beklen
A
A
Department of Medicine/Invärtes medicin, Helsinki University Central Hospital, Helsinki, Finland.
Ainola
M
M
Hukkanen
M
M
Gürgan
C
C
Sorsa
T
T
Konttinen
Y T
YT
D000328:Adult; D000704:Analysis of Variance; D016022:Case-Control Studies; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D005881:Gingiva / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D020381:Interleukin-17 / Q000502:physiology*; D053583:Interleukin-1beta / Q000032:analysis / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D010518:Periodontitis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis*; D015854:Up-Regulation
D020381:Interleukin-17; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases