Anti-inflammatory effects of zinc in PMA-treated human gingival fibroblast cells

Objectives: Abnormal cellular immune response has been considered to be responsible for oral lesions in recurrent aphthous stomatitis. Zinc has been known to be an essential nutrient metal that is necessary for a broad range of biological activities including antioxidant, immune mediator, and anti-inflammatory drugs in oral mucosal disease. The objective of this study was to investigate the effects of zinc in a phorbol-12-myristate-13-acetate (PMA)-treated inflammatory model on human gingival fibroblast cells (hGFs). Study Design: Cells were pre-treated with zinc chloride, followed by PMA in hGFs. The effects were assessed on cell viability, cyclooxygenease-1,2(COX-1/2) protein expression, PGE2 release, ROS production and cytokine release, Results: The effects were assessed on cell viability, COX1/2 protein expression, PGE2 release, ROS production, cytokine release. The results showed that, in the presence of PMA, zinc treatment leads to reduce the production of ROS, which results in decrease of COX-2 expression and PGE2 release. Conclusions: Thus, we suggest that zinc treatment leads to the mitigation of oral inflammation and may prove to be an alternative treatment for recurrent aphthous stomatitis. Key words:Zinc, inflammatory response, cytokines, phorbol-12-myristate-13-acetate, gingival fibroblasts cells.

[1]  Yvonne Bordon.  Innate immunity: A COX detox for the immune system? , 2014, Nature Reviews Immunology.

[2]  Y. Jiménez-Soriano,et al.  Treatment of recurrent aphthous stomatitis. A literature review , 2014, Journal of clinical and experimental dentistry.

[3]  P. Ozturk,et al.  Copper/zinc and copper/selenium ratios, and oxidative stress as biochemical markers in recurrent aphthous stomatitis. , 2013, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[4]  Guojun Zhang,et al.  Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15 , 2013, Mediators of inflammation.

[5]  A. Asakawa,et al.  The role of zinc in the treatment of taste disorders. , 2013, Recent patents on food, nutrition & agriculture.

[6]  J. Liou,et al.  Quiescent Fibroblasts Are More Active in Mounting Robust Inflammatory Responses Than Proliferative Fibroblasts , 2012, PloS one.

[7]  Ying-ying Huang,et al.  Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect , 2012, The Journal of Immunology.

[8]  J. Chiang,et al.  Tumor-Derived Chemokine CCL5 Enhances TGF- b – Mediated Killing of CD8 þ T Cells in Colon Cancer by T-Regulatory Cells , 2012 .

[9]  P. Coyle,et al.  Prenatal exposure to lipopolysaccharide results in neurodevelopmental damage that is ameliorated by zinc in mice , 2012, Brain, Behavior, and Immunity.

[10]  A. Milenović,et al.  Salivary and serum interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha in patients with leukoplakia and oral cancer , 2011, Medicina oral, patologia oral y cirugia bucal.

[11]  J. Dreiher,et al.  Innovative uses for zinc in dermatology. , 2010, Dermatologic clinics.

[12]  J. Haddad.  Thymulin and zinc (Zn2+)-mediated inhibition of endotoxin-induced production of proinflammatory cytokines and NF-kappaB nuclear translocation and activation in the alveolar epithelium: unraveling the molecular immunomodulatory, anti-inflammatory effect of thymulin/Zn2+ in vitro. , 2009, Molecular immunology.

[13]  M. Ashcroft,et al.  Diminished Macrophage Apoptosis and Reactive Oxygen Species Generation after Phorbol Ester Stimulation in Crohn's Disease , 2009, PloS one.

[14]  A. Prasad,et al.  Zinc: role in immunity, oxidative stress and chronic inflammation , 2009, Current opinion in clinical nutrition and metabolic care.

[15]  A. Haberal,et al.  Oxidant/antioxidant status in recurrent aphthous stomatitis. , 2009, Oral diseases.

[16]  D. Kinane,et al.  The host cytokine response to Porphyromonas gingivalis is modified by gingipains. , 2009, Oral microbiology and immunology.

[17]  A. Kerkeni,et al.  Reversal of Cadmium-Induced Thyroid Dysfunction by Selenium, Zinc, or Their Combination in Rat , 2008, Biological Trace Element Research.

[18]  Ş. Karaca,et al.  The effect of gastric Helicobacter pylori eradication on recurrent aphthous stomatitis , 2008, International journal of dermatology.

[19]  E. Ho,et al.  Zinc deficiency alters DNA damage response genes in normal human prostate epithelial cells. , 2008, The Journal of nutrition.

[20]  M. Teixeira,et al.  The Role of Tumor Necrosis Factor Receptor Type 1 in Orthodontic Tooth Movement , 2007, Journal of dental research.

[21]  M. Unalacak,et al.  Purine catabolic enzymes and nitric oxide in patients with recurrent aphthous ulceration. , 2007, Oral diseases.

[22]  K. Kirkwood,et al.  p38 MAPK Signaling in Oral-related Diseases , 2007, Journal of dental research.

[23]  T. Hibi,et al.  Possible inhibitory effect of oral zinc supplementation on hepatic fibrosis through downregulation of TIMP‐1: A pilot study , 2007, Hepatology research : the official journal of the Japan Society of Hepatology.

[24]  R. A. Najim,et al.  Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters , 2007, The Journal of dermatology.

[25]  R. Orbak,et al.  Effects of zinc deficiency on oral and periodontal diseases in rats. , 2007, Journal of periodontal research.

[26]  Christopher M Thomas,et al.  The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. , 2007, Human reproduction update.

[27]  Christine E. Brown,et al.  Tumor-Derived Chemokine MCP-1/CCL2 Is Sufficient for Mediating Tumor Tropism of Adoptively Transferred T Cells1 , 2006, The Journal of Immunology.

[28]  Zoe Diana Draelos,et al.  Zinc and skin health: overview of physiology and pharmacology. , 2006, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[29]  F. Karatas,et al.  Assessment of salivary and serum antioxidant vitamins and lipid peroxidation in patients with recurrent aphthous ulceration. , 2005, The Tohoku journal of experimental medicine.

[30]  A. Kurnatowska,et al.  Predominance of Type 1 cytokines and decreased number of CD4(+)CD25(+high) T regulatory cells in peripheral blood of patients with recurrent aphthous ulcerations. , 2005, Immunology letters.

[31]  C. Kao,et al.  Study of the viral infections and cytokines associated with recurrent aphthous ulceration. , 2005, Microbes and infection.

[32]  G. Garrido,et al.  In vivo and in vitro anti-inflammatory activity of , 2022 .

[33]  R. Kurt,et al.  A dual role for tumor-derived chemokine RANTES (CCL5). , 2003, Immunology letters.

[34]  Marcin Siwek,et al.  Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. , 2003, Polish journal of pharmacology.

[35]  J. Morrow,et al.  The antiangiogenic agent SU5416 down-regulates phorbol ester-mediated induction of cyclooxygenase 2 expression by inhibiting nicotinamide adenine dinucleotide phosphate oxidase activity. , 2003, Cancer research.

[36]  A. Kurnatowska,et al.  Innate immune system is implicated in recurrent aphthous ulcer pathogenesis. , 2003, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[37]  D. Opare Kennedy,et al.  Involvement of intracellular glutathione in zinc deficiency-induced activation of hepatic stellate cells. , 2003, Chemico-biological interactions.

[38]  H. Roth.  Development of alimentary zinc deficiency in growing rats is retarded at low dietary protein levels. , 2003, The Journal of nutrition.

[39]  L. Klotz,et al.  Role of copper, zinc, selenium and tellurium in the cellular defense against oxidative and nitrosative stress. , 2003, The Journal of nutrition.

[40]  S. Liao,et al.  Neurotrophic and neurotoxic effects of zinc on neonatal cortical neurons , 2003, Neurochemistry International.

[41]  P. Coyle,et al.  Zinc treatment prevents lipopolysaccharide-induced teratogenicity in mice. , 2003, Birth defects research. Part A, Clinical and molecular teratology.

[42]  Y. Çiçek,et al.  Effects of zinc treatment in patients with recurrent aphthous stomatitis. , 2003, Dental materials journal.

[43]  L. Ng,et al.  Neutrophil activation and production of reactive oxygen species in pre-eclampsia , 2003, Journal of hypertension.

[44]  F. Martinon,et al.  NALPs: a novel protein family involved in inflammation , 2003, Nature Reviews Molecular Cell Biology.

[45]  H. Ljunggren,et al.  Variable expression of Toll-like receptor in murine innate and adaptive immune cell lines. , 2002, International immunology.

[46]  H. Bruunsgaard,et al.  Identification of IFN-γ-Producing CD4+ T Cells Following PMA Stimulation , 2001 .

[47]  F. Branca,et al.  Reduced growth and skeletal changes in zinc-deficient growing rats are due to impaired growth plate activity and inanition. , 2001, The Journal of nutrition.

[48]  G. Seymour,et al.  Cytokines in periodontal disease: where to from here? , 2001, Acta odontologica Scandinavica.

[49]  M. Ridley,et al.  Aphthous ulcers: a difficult clinical entity. , 2000, American journal of otolaryngology.

[50]  B. Moore,et al.  Identification of an IFN‐γ responsive region in an intron of the invariant chain gene , 2000 .

[51]  G. FitzGerald,et al.  Effect of regulated expression of human cyclooxygenase isoforms on eicosanoid and isoeicosanoid production in inflammation. , 2000, The Journal of clinical investigation.

[52]  M. Sogorb,et al.  Dichlorophenyl phosphoramidates as substrates for avian and mammalian liver phosphotriesterases: activity levels, calcium dependence and stereospecificity. , 1999, Chemico-biological interactions.

[53]  S. Dundar.  Recurrent Aphthous Stomatitis , 1987, The Australasian journal of dermatology.

[54]  F. Keleştimur,et al.  Pubertal arrest due to Zn deficiency: the effect of zinc supplementation. , 2007, Hormones.

[55]  D. Fivenson.  The mechanisms of action of nicotinamide and zinc in inflammatory skin disease. , 2006, Cutis.

[56]  H. Bruunsgaard,et al.  Identification of IFN-gamma-producing CD4+ T cells following PMA stimulation. , 2001, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[57]  C. Chang,et al.  Identification of an IFN-gamma responsive region in an intron of the invariant chain gene. , 2000, European journal of immunology.

[58]  H. Lodish.  Molecular Cell Biology , 1986 .