Pro-inflammatory properties of cadmium
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Cadmium is a toxic and carcinogenic heavy metal that nowadays constitutes a serious environmental health problem. The aim of this study is to review the effects of cadmium on selected inflammatory mediators and markers, such as NF-κB and AP-1 transcription factors, IL-6, TNF-α, IL-1β cytokines, IL-8 or MIP-2 chemokine, MPO, iNOS, MMPs and COX-2 enzymes, PGE2 (product of COX-2 enzyme), ICAM-1, VCAM-1 and PECAM-1 adhesion molecules, and CRP. The research strategy identified articles available in Medline, published between 1998 and 2012; we included both in vivo and in vitro studies carried out on humans and rodents. Most of the reviewed research findings suggest that cadmium in micromolar concentrations (especially in the 1-10 μM range) causes up-regulation of the mediators and markers of inflammation, and appears to have pro-inflammatory properties. However, it is worth mentioning that a contradictory or even opposite hypothesis exists, which suggests cadmium to be an anti-inflammatory factor. Further research including detailed histological analyses should solve this discrepancy. Nevertheless, it appears that the main reason for these contradictory findings is the experimental setup: different biological systems analyzed and different doses of cadmium applied.
- Department of Hygiene, Epidemiology and Public Health, Pomeranian Medical University, Szczecin, Poland
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
- Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
- Afolabi OK, Oyewo EB, Adekunle AS, Adedosu OT, Adedeji AL (2012) Impaired lipid levels and inflammatory response in rats exposed to cadmium. EXCLI J 11: 677-687.
- Alvarez SM, Gómez NN, Scardapane L, Zirulnik F, Martínez D, Giménez MS (2004) Morphological changes and oxidative stress in rat prostate exposed to a non-carcinogenic dose of cadmium. Toxicol Lett 153: 365-376.
- Bernhard D, Rossmann A, Henderson B, Kind M, Seubert A, Wick G (2006) Increased serum cadmium and strontium levels in young smokers: effects on arterial endothelial cell gene transcription. Arterioscler Thromb Vasc Biol 26: 833-838.
- Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88: 1549-1559.
- Choi J, Chang H, Rhee S (2002) Effect of green tea catechin on arachidonic acid cascade in chronic cadmium-poisoned rats. Asia Pac J Clin Nutr 11: 292-297.
- Cormet-Boyaka E, Jolivette K, Bonnegarde-Bernard A, Rennolds J, Hassan F, Mehta P, Tridandapani S, Webster-Marketon J, Boyaka PN (2012) An NF-κB-independent and Erk1/2-dependent mechanism controls CXCL8/IL-8 responses of airway epithelial cells to cadmium. Toxicol Sci 125: 418-429.
- Cuypers A, Plusquin M, Remans T, Jozefczak M, Keunen E, Gielen H, Opdenakker K, Nair AR, Munters E, Artois TJ, Nawrot T, Vangronsveld J, Smeets K (2010) Cadmium stress: an oxidative challenge. Biometals 23: 927-940.
- Czeczot H, Skrzycki M (2010) Cadmium - element completely unnecessary for the organism. Postepy Hig Med Dosw 64: 38-49.
- Das UN (2011) Inflammation. In: Molecular Basis of Health and Disease. Das UN, ed, pp 15-100. Springer Science+Business Media BV.
- Dong W, Simeonova P, Gallucci R, Matheson J, Flood L, Wang S, Hubbs A, Luster MI (1998) Toxic metals stimulate inflammatory cytokines in hepatocytes through oxidative stress mechanisms. Toxicol Appl Pharmacol 151: 359-366.
- Fievez L, Kirschvink N, Zhang WH, Lagente V, Lekeux P, Bureau F, Gustin P (2009) Effects of betamethasone on inflammation and emphysema induced by cadmium nebulisation in rats. Eur J Pharmacol 606: 210-214.
- Figueiredo-Pereira ME, Li Z, Jansen M, Rockwell P (2002) N-acetylcysteine and celecoxib lessen cadmium cytotoxicity which is associated with cyclooxygenase-2 up-regulation in mouse neuronal cells. J Biol Chem 277: 25283-25289.
- Fowler BA (2009) Monitoring of human populations for early markers of cadmium toxicity: a review. Toxicol Appl Pharmacol 238: 294-300.
- Freitas M, Fernandes E (2011) Zinc, cadmium and nickel increase the activation of NF-κB and the release of cytokines from THP-1 monocytic cells. Metallomics 3:1238-1243.
- Go YM, Orr M, Jones DP (2012) Increased nuclear thioredoxin-1 potentiates cadmium-induced cytotoxicity. Toxicol Sci, doi: 10.1093/toxsci/kfs271.
- Godt J, Scheidig F, Grosse-Siestrup C, Esche V, Brandenburg P, Reich A, Groneberg DA (2006) The toxicity of cadmium and resulting hazards for human health. J Occup Med Toxicol 1: 22.
- Haase H, Ober-Blöbaum JL, Engelhardt G, Hebel S, Rink L (2010) Cadmium ions induce monocytic production of tumor necrosis factor-alpha by inhibiting mitogen activated protein kinase dephosphorylation. Toxicol Lett 198: 152-158.
- Hart BA, Lee CH, Shukla GS, Shukla A, Osier M, Eneman JD, Chiu JF (1999) Characterization of cadmium-induced apoptosis in rat lung epithelial cells: evidence for the participation of oxidant stress. Toxicology 133: 43-58.
- Hsu CW, Lin JL, Lin-Tan DT, Yen TH, Huang WH, Ho TC, Huang YL, Yeh LM, Huang LM (2009) Association of environmental cadmium exposure with inflammation and malnutrition in maintenance haemodialysis patients. Nephrol Dial Transplant 24: 1282-1288.
- International Agency for Research on Cancer (2012) Cadmium and cadmium compounds. In: Arsenic, metals, fibres and dusts. A review of human carcinogens. IARC Monographs 100C, pp 121-145. IARC, Lyon, France.
- Jarup L (2002) Cadmium overload and toxicity. Nephrol Dial Transplant 17 (suppl 2): 35-39.
- Jarup L, Akesson A (2009) Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol 238: 201-208.
- Jeong EM, Moon CH, Kim CS, Lee SH, Baik EJ, Moon CK, Jung YS (2004) Cadmium stimulates the expression of ICAM-1 via NF-kappaB activation in cerebrovascular endothelial cells. Biochem Biophys Res Commun 320: 887-892.
- Jiang J, McCool BA, Parrish AR (2002) Cadmium- and mercury-induced intercellular adhesion molecule-1 expression in immortalized proximal tubule cells: evidence for a role of decreased transforming growth factor-beta1. Toxicol Appl Pharmacol 179: 13-20.
- Kataranovski M, Mirkov I, Belij S, Nikolic M, Zolotarevski L, Ciric D, Kataranovski D. (2009) Lungs: remote inflammatory target of systemic cadmium administration in rats. Environ Toxicol Pharmacol 28: 225-231.
- Kirschvink N, Vincke G, Fiévez L, Onclinx C, Wirth D, Belleflamme M, Louis R, Cataldo D, Peck MJ, Gustin P (2005) Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and emphysema in rats. Toxicology 211: 36-48.
- Klaassen CD, Liu J, Diwan BA (2009) Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol 238: 215-220.
- Knoflach M, Messner B, Shen YH, Frotschnig S, Liu G, Pfaller K, Wang X, Matosevic B, Willeit J, Kiechl S, Laufer G, Bernhard D (2011) Non-toxic cadmium concentrations induce vascular inflammation and promote atherosclerosis. Circ J 75: 2491-2495.
- Kundu S, Sengupta S, Bhattacharyya A (2011) EGFR upregulates inflammatory and proliferative responses in human lung adenocarcinoma cell line (A549), induced by lower dose of cadmium chloride. Inhal Toxicol 23: 339-348.
- Kundu S, Sengupta S, Chatterjee S, Mitra S, Bhattacharyya A (2009) Cadmium induces lung inflammation independent of lung cell proliferation: a molecular approach. J Inflamm 6: 19.
- Lag M, Rodionov D, Ovrevik J, Bakke O, Schwarze PE, Refsnes M (2010) Cadmium-induced inflammatory responses in cells relevant for lung toxicity: Expression and release of cytokines in fibroblasts, epithelial cells and macrophages. Toxicol Lett 193: 252-260.
- Lee J, Lim KT (2011) Preventive effect of phytoglycoprotein (27 kDa) on inflammatory factors at liver injury in cadmium chloride-exposed ICR mice. J Cell Biochem 112: 694-703.
- Lee J, Lim K (2011) Inhibitory effect of plant-originated glycoprotein (27 kDa) on expression of matrix metalloproteinase-9 in cadmium chloride-induced BNL CL.2 cells. J Trace Elem Med Biol 25: 239-246.
- Lin YS, Rathod D, Ho WC, Caffrey JJ (2009) Cadmium exposure is associated with elevated blood C-reactive protein and fibrinogen in the U. S. population: the third national health and nutrition examination survey (NHANES III, 1988-1994). Ann Epidemiol 19: 592-596.
- Martynowicz H, Skoczyńska A (2003) Effects of cadmium on the vascular endothelium function. Med Pr 54: 383-388.
- Messner B, Bernhard D (2010) Cadmium and cardiovascular diseases: cell biology, pathophysiology, and epidemiological relevance. Biometals 23: 811-822.
- Miyahara T, Katoh T, Watanabe M, Mikami Y, Uchida S, Hosoe M, Sakuma T, Nemoto N, Takayama K, Komurasaki T (2004) Involvement of mitogen-activated protein kinases and protein kinase C in cadmium-induced prostaglandin E2 production in primary mouse osteoblastic cells. Toxicology 200: 159-167.
- Miyahara T, Tonoyama H, Watanabe M, Okajima A, Miyajima S, Sakuma T, Nemoto N, Takayama K (2001) Stimulative effect of cadmium on prostaglandin E2 production in primary mouse osteoblastic cells. Calcif Tissue Int 68: 185-191.
- Mlynek V, Skoczyńska A (2005) The pro-inflammatory activity of cadmium. Postepy Hig Med Dosw 59: 1-8.
- Mousa SA (2004) Expression of adhesion molecules during cadmium hepatotoxicity. Life Sci 75: 93-105.
- Park SL, Kim YM, Ahn JH, Lee SH, Baik EJ, Moon CH, Jung YS (2009) Cadmium stimulates the expression of vascular cell adhesion molecule-1 (VCAM-1) via p38 mitogen-activated protein kinase (MAPK) and JNK activation in cerebrovascular endothelial cells. J Pharmacol Sci 110: 405-409.
- Prozialeck WC, Edwards JR, Woods JM (2006) The vascular endothelium as a target of cadmium toxicity. Life Sci 79: 1493-1506.
- Ramirez DC, Gimenez MS (2003) Induction of redox changes, inducible nitric oxide synthase and cyclooxygenase-2 by chronic cadmium exposure in mouse peritoneal macrophages. Toxicol Lett 145: 121-132.
- Rennolds J, Malireddy S, Hassan F, Tridandapani S, Parinandi N, Boyaka PN, Cormet-Boyaka E (2012) Curcumin regulates airway epithelial cell cytokine responses to the pollutant cadmium. Biochem Biophys Res Commun 417: 256-261.
- Rockwell P, Martinez J, Papa L, Gomes E (2004) Redox regulates COX-2 upregulation and cell death in the neuronal response to cadmium. Cell Signal 16: 343-353.
- Romare A, Lundholm CE (1999) Cadmium-induced calcium release and prostaglandin E2 production in neonatal mouse calvaria are dependent on cox-2 induction and protein kinase C activation. Arch Toxicol 73: 223-228.
- Seok SM, Park DH, Kim YC, Moon CH, Jung YS, Baik EJ, Moon CK, Lee SH (2006) COX-2 is associated with cadmium-induced ICAM-1 expression in cerebrovascular endothelial cells. Toxicol Lett 165: 212-220.
- Shin HJ, Park KK, Lee BH, Moon CK, Lee MO (2003) Identification of genes that are induced after cadmium exposure by suppression subtractive hybridization. Toxicology 191: 121-131.
- Souza V, Escobar Md Mdel C, Gómez-Quiroz L, Bucio L, Hernández E, Cossio EC, Gutiérrez-Ruiz MC (2004) Acute cadmium exposure enhances AP-1 DNA binding and induces cytokines expression and heat shock protein 70 in HepG2 cells. Toxicology 197: 213-228.
- Stosic J, Mirkov I, Belij S, Nikolic M, Popov A, Kataranovski D, Kataranovski M (2010) Gender differences in pulmonary inflammation following systemic cadmium administration in rats. Biomed Environ Sci 23: 293-299.
- Tracey KJ (2002) The inflammatory reflex. Nature 420: 853-859.
- Valko M, Morris H, Cronin MT (2005) Metals, Toxicity and Oxidative Stress. Curr Med Chem 12: 1161-1208.
- Yaghooti H, Firoozrai M, Khorramizadeh MR (2012) Acute cadmium exposure augments MMP-9 secretion and disturbs MMP-9/TIMP-1 balance. Asian Biomed 6: 445-451.
- Yang Z, Yang S, Qian SY, Hong JS, Kadiiska MB, Tennant RW, Waalkes MP, Liu J (2007) Cadmium-induced toxicity in rat primary mid-brain neuroglia cultures: role of oxidative stress from microglia. Toxicol Sci 98: 488-494.
- Yazıhan N, Koçak MK, Akçıl E, Erdem O, Sayal A, Güven C, Akyürek N (2011) Involvement of galectin-3 in cadmium-induced cardiac toxicity. Anadolu Kardiyol Derg 11: 479-484.
- Zhao Z, Hyun JS, Satsu H, Kakuta S, Shimizu M (2006) Oral exposure to cadmium chloride triggers an acute inflammatory response in the intestines of mice, initiated by the over-expression of tissue macrophage inflammatory protein-2 mRNA. Toxicol Lett 164: 144–154.
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