Circulating Interleukin‐6 and High‐Sensitivity C‐Reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects

Marcaccini, Andrea M.; Meschiari, César A.; Sorgi, Carlos Artério; Saraiva, Maria da Conceição Pereira; Souza, Ana Maria de; Faccioli, Lúcia Helena; Tanus‐Santos, José Eduardo; Novaes, Arthur B.; Gerlach, Raquel Fernanda

doi:10.1902/jop.2009.080561

Cited by 119 publications

(116 citation statements)

References 61 publications

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“…Níveis circulantes aumentados de diversos marcadores inflamatórios em pacientes com DP e a diminuição desses níveis após o tratamento periodontal não cirúrgico sustentam essa hipótese (Marcaccini, Meschiari et al 2009). …”

Section: Doença Periodontalunclassified

“…Já estão descritas as correlação de moléculas endógenas como citocinas, prostaglandinas, anticorpos, hormônios, MMPs, TIMPs, fator tecidual, ácido siálico entre saliva total e plasma (Greabu, Battino et al 2009;Marcaccini, Meschiari et al 2009;Emekli-Alturfan, Basar et al 2011;Oktay, Basar et al 2011). A saliva também pode ser utilizada para detectar substâncias exógenas como medicamentos e drogas de abuso, podendo também, detectar a infecção por microrganismos (vírus, bactérias e fungos), através da presença de proteínas e DNA microbianos, ou anticorpos do hospedeiro contra esses patógenos.…”

Section: Saliva E Biomarcadoresunclassified

“…-Solução de acrilamida 30% e bisacrilamida (0,8%); A seleção dos pacientes, diagnóstico e tratamento da DP foram realizados de acordo com (Marcaccini, Meschiari et al 2009;Marcaccini, Novaes et al 2009). …”

Section: Soluções Utilizadas Nos Experimentosunclassified

“…Marcacinni et al (Marcaccini, Meschiari et al 2009) demonstram que a DP leva ao aumento de marcadores inflamatórios sistêmicos nestes pacientes; a proteína C reativa, por exemplo, é produzida no fígado (Genest 2010). Como estes marcadores inflamatórios (IL-6 e hs-CRP) estão aumentados, é bastante razoável imaginar que também a expressão e secreção de MMP-8 e -9 poderiam estar aumentadas em outros tipos celulares, tais como macrófagos e células endoteliais.…”

Section: Steunclassified

“…Uma possível explicação para este fenômeno seria a ação dos sinalizadores inflamatórios aumentados sistemicamente pela DP (Marcaccini, Meschiari et al 2009), tais como as citocinas, que agiriam de maneira semelhante nas células destes dois compartimentos aparentemente distintos, promovendo o aumento da expressão de MMP-9 nos dois compartimentos.…”

Section: Ste Versus Plasmaunclassified

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Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma

Meschiari¹

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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases known to cleave components of the connective tissue in physiological and pathological processes. The regulation of MMP activities is done by the tissue inhibitors of metalloproteinases (TIMPs).Periodontal disease (PD) is a chronic inflammation with excessive activity of MMPs, which degrade the tooth supporting tissues.The saliva components are derived from the local blood supply, and this fluid may therefore reflect the plasma. So, the objectives of this study were: 1) to compare the levels of MMPs, TIMPs and MPO in stimulated whole saliva (SWS) and plasma of PD patients before (PB) and 3 months after (PT) the non-surgical periodontal treatment, and in healthy volunteers at baseline (CB) and 3 months after baseline (CT), and 2) to evaluate the correlations between the results found.Measurements of MMP-8, MMP-9, TIMP-1 and TIMP-2 were performed by ELISA. Gelatinolitic activity of MMP-9 forms were determined by zymography, and the MPO activity was determined by colorimetric assay.There was lower gelatinolitic activity, and lower concentrations of MMP-8 and TIMP-2 in STE on PT group compared with PB group (p <0.05). MPO activity was higher in PB compared to CB (p <0.05).Statistically significant moderate correlations were observed in all associations between MMP-9 performed by ELISA in plasma and gelatinolitic activity bands of STE: MMP-9 molecular form of 92 kDa (r = 0,37, p = 0,0017), MMP-9 molecular form of 130 kDa (r = 0,35, p = 0,003), the sum of its gelatinase activity (130 +92 kDa) (r = 0,43, p = 0,0002), gelatinase of 180 kDa (r = 0,35, p = 0,003), and the sum of total gelatinase activity (180+130+92 kDa) (r = 0,37, p = 0,002). Circulating MMP-8 levels correlate with salivary gelatinase activity bands of 92 kDa (r = 0,30, p = 0,01) and the sum of gelatinase activity (130 +92 kDa) (r = 0,24, p = 0,04). In addition, a weak correlation between gelatinase activity of plasmatic 92 kDa MMP-9 and gelatinase of 180 kDa in SWS (r= 0,26 p = 0,03) was found, and a moderate correlation between plasmatic TIMP-2 and TIMP-2 of SWS (r = 0,32, p = 0,004).The results show that the gelatinase activity of SWS may reflect the concentrations of systemic inflammatory markers such as MMP-8 and MMP-9, also the concentration of TIMP-2 in the SWS may reflect the circulating concentration of TIMP-2. The evaluation of these results suggests that there is an attenuation of some inflammatory markers analyzed in the SWS and in plasma after treatment of PD. Furthermore, there are correlations between salivary and plasma levels in some of these markers. Because saliva sampling is less invasive, more studies about the correlations between these markers in these two fluids are necessary. Key words: saliva, plasma, matrix metalloproteinases, periodontal disease. LISTA DE ABREVIATURAS, SIGLAS E SÍMBOLOS BSA -

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Section: Doença Periodontalunclassified

Section: Saliva E Biomarcadoresunclassified

Section: Soluções Utilizadas Nos Experimentosunclassified

Section: Steunclassified

Section: Ste Versus Plasmaunclassified

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Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma

Meschiari¹

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IL‐6 and high glucose synergistically upregulate MMP‐1 expression by U937 mononuclear phagocytes via ERK1/2 and JNK pathways and c‐Jun

Samuvel

Sundararaj

et al. 2010

J of Cellular Biochemistry

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Matrix metalloproteinases (MMPs) play a pivotal role in tissue remodeling and destruction in inflammation-associated diseases such as cardiovascular disease and periodontal disease. Although it is known that interleukin (IL)-6 is a key proinflamatory cytokine, it remains unclear how IL-6 regulates MMP expression by mononuclear phagocytes. Furthermore, it remains undetermined how IL-6 in combination with hyperglycemia affects MMP expression. In the present study, we investigated the regulatory effect of IL-6 alone or in combination with high glucose on MMP-1 expression by U937 mononuclear phagocytes. We found that IL-6 is a powerful stimulator for MMP-1 expression and high glucose further augmented IL-6-stimulated MMP-1 expression. We also found that high glucose, IL-6, and lipopolysaccharide act in concert to stimulate MMP-1 expression. In the studies to elucidate underlying mechanisms, the extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) pathways were found to be required for stimulation of MMP-1 by IL-6 and high glucose. We also observed that IL-6 and high glucose stimulated the expression of c-Jun, a key subunit of AP-1 known to be essential for MMP-1 transcription. The role of c-Jun in MMP-1 expression was confirmed by the finding that suppression of c-Jun expression by RNA interference significantly inhibited MMP-1 expression. Finally, we demonstrated that similarly to U937 mononuclear phagocytes, IL-6 and high glucose also stimulated MMP-1 secretion from human primary monocytes. In conclusion, this study demonstrated that IL-6 and high glucose synergistically stimulated MMP-1 expression in mononuclear phagocytes via ERK and JNK cascades and c-Jun upregulation. KeywordsMatrix metalloproteinases; Interleukin 6; Diabetes; Mitogen-activated protein kinases Interleukin-6 (IL-6) is a multifunctional cytokine involved in the acute phase response, immunity, hematopoiesis, and inflammation [Ishihara and Hirano, 2002;Kishimoto, 2006]. IL-6 plays an essential role in many chronic inflammatory diseases such as rheumatoid arthritis, systemic-onset juvenile chronic arthritis, osteoporosis, psoriasis, and autoimmune diseases such as antigen-induced arthritis and experimental allergic encephalomyelitis [Ishihara and Hirano, 2002]. IL-6 is also important in the pathogenesis of infectious diseases such as periodontal disease [Geivelis et al., 1993;Rusconi et al., 1991]. Furthermore, IL-6 is a marker for cardiovascular disease [Kristiansen and Mandrup-Poulsen, 2005;Rattazzi et al., 2003], which is considered as an inflammatory disease. Studies have well documented that the plasma levels of IL-6 and C-reactive protein are strong independent predictors of risk of future cardiovascular events, both in patients with a history of coronary heart disease and in apparently healthy subjects [Rattazzi et al., 2003]. Numerous studies have further demonstrated that IL-6 is not just a marker for inflammation-associated diseases; it is a major player involved in the initiation and progression of the d...

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Periodontal disease and its connection to systemic biomarkers of cardiovascular disease in young American Indian/Alaskan natives

Delange

Lindsay

Lemus

et al. 2018

Journal of Periodontology

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Circulating Interleukin‐6 and High‐Sensitivity C‐Reactive Protein Decrease After Periodontal Therapy in Otherwise Healthy Subjects

Cited by 119 publications

References 61 publications

Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma

Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma

IL‐6 and high glucose synergistically upregulate MMP‐1 expression by U937 mononuclear phagocytes via ERK1/2 and JNK pathways and c‐Jun

Periodontal disease and its connection to systemic biomarkers of cardiovascular disease in young American Indian/Alaskan natives

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