MMPs, IL-1, and TNF are Regulated by IL-17 in Periodontitis

Abstract

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.

Constitutive expression of MMP9 in intestinal epithelium worsens murine acute colitis and is associated with increased levels of proinflammatory cytokine Kc

“…A direct interaction between MMP9 and IL-8 has been reported in hematopoietic stem cell trafficking in liver injury (17,20), in retinoic acid syndrome (45), and in leucocytes (51). Beklen et al (7) showed that there was an upregulation of both MMP9 and IL-8 in periodontitis. Many studies related with airway epithelium have shown a direct link between the IL-8 secretion and MMP9 expression (15,31,55).…”

A Deficiência de vitamina d está associada com níveis aumentados de il-17 e tnfα em pacientes com insuficiência cardíaca crônica

“…Novel proinflammatory cytokine IL-17 has recently become implicated in CHF 10 . Animal models demonstrated that IL-17 is essential for the development of dilated cardiomyopathy, probably by stimulating fibrosis through direct and/or indirect induction of MMP1/2/3/9 10,11 . IL-17 is also required for the sustained expression of IL-6 during myocarditis 27 .…”

“…The neutralization of IL-17 reduces myocarditis severity 9 and has an essential role in the development of dilated cardiomyopathy 10 . Th17 cells infiltrate the inflamed heart and are responsible for heart-specific up-regulation of IL-6, TNFα, IL-1β, which can promote fibrosis, either directly or indirectly, by inducting matrix metal proteases 1, 2, 3 and 9 10,11 . Moreover, TNFα and IL-17 act synergistically to create a proinflammatory environment 12 .…”

Cyclic AMP Response Element-binding Protein H (CREBH) Mediates the Inhibitory Actions of Tumor Necrosis Factor α in Osteoblast Differentiation by Stimulating Smad1 Degradation

“…Inflammatory cytokines inhibit BMP-induced osteogenesis and bone formation (17,18); in fact, TNF␣ is a major inflammatory mediator responsible for bone loss in a number of bonerelated inflammatory diseases (19,20). TNF␣ inhibits BMP signaling by interfering with the DNA-binding ability of Smads via activation of the nuclear factor-B (NF-B) pathway, regulating Runx2 expression, and inhibiting BMP-induced osteoblast differentiation (18,21,22).…”