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Oxidative stress-induced inflammatory responses and effects of N-acetylcysteine in bovine mammary alveolar cells

Published online by Cambridge University Press:  20 November 2017

Hyojin Bae ,
Chang Hee Jeong ,
Wei Nee Cheng ,
Kwonho Hong ,
Han Geuk Seo  and
Sung Gu Han
Hyojin Bae
Affiliation:
Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea
Chang Hee Jeong
Affiliation:
Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea
Wei Nee Cheng
Affiliation:
Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea
Kwonho Hong
Affiliation:
Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea
Han Geuk Seo
Affiliation:
Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea
Sung Gu Han*
Affiliation:
Department of Food Science and Biotechnology of Animal Resources, Konkuk University, Seoul 05029, Republic of Korea
*
*For correspondence; e-mail: hansg@konkuk.ac.kr
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Abstract

Bovine mastitis, an inflammation of the udder, results in reduced milk production and poor milk quality. Mastitis is usually, but not always, a response to pathogen infection. High milk yield can produce oxidative stress in the mammary tissue. High milk yield is also known to be associated with bovine mastitis. Thus, in the current study, we hypothesised that oxidative stress increases inflammatory responses in bovine mammary cells. To examine the hypothesis, we produced cellular oxidative stress and investigated resulting inflammatory responses in bovine mammary alveolar cells (MAC-T). To produce oxidative stress, cells were treated with the reactive oxygen species (ROS; e.g., superoxide anion)-producing agent, menadione (MD; 0–10 µm; 6 h). To ensure the ROS-induced responses, cells were pretreated with an antioxidant NAC (0–10 mm; 1 h). Results showed that MD elevated intracellular ROS levels and protein expression of cyclooxygenase-2 (COX-2), a biomarker of inflammation. Pretreatment of cells with NAC attenuated MD-induced COX-2 expression by scavenging intracellular ROS and enhancing intracellular glutathione levels. MD-induced COX-2 expression was mediated by activation of extracellular signal receptor-activated kinase 1/2 (ERK1/2), Akt, and nuclear factor-kappa B (NF-κB). NAC attenuated activation of these intracellular signalling molecules. Treatment of cells with pharmacological inhibitors for ERK1/2, Akt, and NF-κB confirmed the association of these signalling pathways in MD-induced COX-2 expression. These results support our hypothesis that oxidative stress, which is found in high-yielding dairy cows, can produce cellular inflammation in bovine mammary alveolar cells and prevention of oxidative stress can attenuate such pathological responses. This may be relevant for cases of clinical mastitis for which no pathogen can be isolated.

Keywords

Oxidative stressmastitisinflammationcyclooxygenase-2MAC-T cells

Information

Type
Research Article
Information
Journal of Dairy Research , Volume 84 , Issue 4 , November 2017 , pp. 418 - 425
Copyright
Copyright © Hannah Research Foundation 2017 

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References

Cargnello, M & Roux, PP 2011 Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiology and Molecular Biology Reviews 75 50–83 Google Scholar
Castillo, C, Hernandez, J, Valverde, I, Pereira, V, Sotillo, J, Alonso, ML & Benedito, J 2006 Plasma malonaldehyde (MDA) and total antioxidant status (TAS) during lactation in dairy cows. Research in Veterinary Science 80 133–139 Google Scholar
Chassagne, M, Barnouin, J & Chacornac, JP 1998 Biological predictors for early clinical mastitis occurrence in Holstein cows under field conditions in France. Preventive Veterinary Medicine 35 29–38 Google Scholar
Chung, M-H, Kim, D-H, Na, H-K, Kim, J-H, Kim, H-N, Haegeman, G & Surh, Y-J 2014 Genistein inhibits phorbol ester-induced NF-κB transcriptional activity and COX-2 expression by blocking the phosphorylation of p65/RelA in human mammary epithelial cells. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 768 74–83 Google Scholar
Corl, C, Robinson, H, Contreras, G, Holcombe, S, Cook, V & Sordillo, L 2010 Ethyl pyruvate diminishes the endotoxin-induced inflammatory response of bovine mammary endothelial cells. Journal of Dairy Science 93 5188–5199 Google Scholar
De, U & Mukherjee, R 2014 Activity of cyclooxygenase-2 and nitric oxide in milk leucocytes following intramammary inoculation of a bio-response modifier during bovine Staphylococcus aureus subclinical mastitis. Veterinary Research Communications 38 201–207 CrossRefGoogle ScholarPubMed
Decoursey, T & Ligeti, E 2005 Regulation and termination of NADPH oxidase activity. Cellular and Molecular Life Sciences 62 2173–2193 Google Scholar
Deferme, L, Briede, J, Claessen, S, Cavill, R & Kleinjans, J 2015 Cell line-specific oxidative stress in cellular toxicity: A toxicogenomics-based comparison between liver and colon cell models. Toxicology in Vitro 29 845–855 Google Scholar
Halasi, M, Wang, M, Chavan, TS, Gaponenko, V, Hay, N & Gartel, AL 2013 ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors. Biochemical Journal 454 201–208 Google Scholar
Jeong, CH, Seok, JS, Petriello, MC & Han, SG 2017 Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29. Toxicology 379 31–39 Google Scholar
Jin, L, Yan, S, Shi, B, Sheng, R, Shi, H, Zhao, Y & Li, J 2016a Effects of retinoic acid on the synthesis of selenoprotein and the antioxidative indices of bovine mammary epithelial cells in vitro. Czech Journal of Animal Science 61 194–202 Google Scholar
Jin, X, Wang, K, Liu, H, Hu, F, Zhao, F & Liu, J 2016b Protection of bovine mammary epithelial cells from hydrogen peroxide-induced oxidative cell damage by resveratrol. Oxidative Medicine and Cellular Longevity 2016 2572175 Google Scholar
Jozwik, A, Krzyzewski, J, Strzalkowska, N, Polawska, E, Bagnicka, E, Wierzbicka, A, Niemczuk, K, Lipinska, P & Horbanczuk, JO 2012 Relations between the oxidative status, mastitis, milk quality and disorders of reproductive functions in dairy cows – a review. Animal Science Papers and Reports 30 297–307 Google Scholar
Kang, S, Lee, JS, Lee, HC, Petriello, MC, Kim, BY, Do, JT, Lim, DS, Lee, HG & Han, SG 2016 Phytoncide extracted from pinecone decreases LPS-induced inflammatory responses in bovine mammary epithelial cells. Journal of Microbiology and Biotechnology 26 579–587 Google Scholar
Kim, H-N, Kim, D-H, Kim, E-H, Lee, M-H, Kundu, JK, Na, H-K, Cha, Y-N & Surh, Y-J 2014a Sulforaphane inhibits phorbol ester-stimulated IKK-NF-κB signaling and COX-2 expression in human mammary epithelial cells by targeting NF-κB activating kinase and ERK. Cancer Letters 351 41–49 Google Scholar
Kim, YJ, Shin, YK, Sohn, DS & Lee, CS 2014b Menadione induces the formation of reactive oxygen species and depletion of GSH-mediated apoptosis and inhibits the FAK-mediated cell invasion. Naunyn-Schmiedeberg Archiv für Pharmakologie 387 799–809 Google Scholar
Liu, C-M, Sun, Y-Z, Sun, J-M, Ma, J-Q & Cheng, C 2012 Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-κB pathway. Biochimica et Biophysica Acta (BBA)-General Subjects 1820 1693–1703 Google Scholar
Liu, L, Lin, Y, Liu, L, Bian, Y, Zhang, L, Gao, X & Li, Q 2015 14-3-3γ regulates lipopolysaccharide-induced inflammatory responses and lactation in dairy cow mammary epithelial cells by inhibiting NF-κB and MAPKs and up-regulating mTOR signaling. International Journal of Molecular Sciences 16 16622–16641 Google Scholar
Loboda, A, Damulewicz, M, Pyza, E, Jozkowicz, A & Dulak, J 2016 Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cellular and Molecular Life Sciences 73 3221–3247 Google Scholar
Lohrke, B, Viergutz, T, Kanitz, W, Gollnitz, K, Becker, F, Hurtienne, A & Schweigert, F 2004 High milk yield in dairy cows associated with oxidant stress. Online Journal of Veterinary Research 8 70–78 Google Scholar
Ma, Q 2013 Role of nrf2 in oxidative stress and toxicity. Annual Review of Pharmacology and Toxicology 53 401–426 Google Scholar
O'Reilly, KM, Green, MJ, Peeler, EJ, Fitzpatrick, JL & Green, LE 2006 Investigation of risk factors for clinical mastitis in British dairy herds with bulk milk somatic cell counts less than 150,000 cells/ml. Veterinary Record 15 649–653 Google Scholar
Poławska, E, Bagnicka, AW, Niemczuk, K & Lipińska, JO 2012 Relations between the oxidative status, mastitis, milk quality and disorders of reproductive functions in dairy cows – a review. Animal Science Papers and Reports 30 297–307 Google Scholar
Rahman, I & MacNee, W 2000 Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radical Biology and Medicine 28 1405–1420 Google Scholar
Reshi, AA, Husain, I, Bhat, S, Rehman, MU, Razak, R, Bilal, S & Mir, MR 2015 Bovine mastitis as an evolving disease and its impact on the dairy industry. International Journal of Current Research and Review 7 48–55 Google Scholar
Ricciotti, E & FitzGerald, GA 2011 Prostaglandins and inflammation. Arteriosclerosis, Thrombosis and Vascular Biology 31 986–1000 Google Scholar
Ryter, SW, Alam, J & Choi, AM 2006 Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiological Reviews 86 583–650 Google Scholar
Sadowska, A, Manuel-Y-Keenoy, B & De Backer, W 2007 Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulmonary Pharmacology & Therapeutics 20 9–22 Google Scholar
Shi, H, Yan, S, Jin, L, Shi, B & Guo, X 2016 Vitamin A affects the expression of antioxidant genes in bovine mammary epithelial cells with oxidative stress induced by diethylene triamine-nitric oxide polymer. Czech Journal of Animal Science 61 117–126 Google Scholar
Sordillo, LM & Aitken, SL 2009 Impact of oxidative stress on the health and immune function of dairy cattle. Veterinary Immunology and Immunopathology 12 104–109 CrossRefGoogle Scholar
Sun, S-Y 2010 N-acetylcysteine, reactive oxygen species and beyond. Cancer Biology & Therapy 9 109–110 Google Scholar
Torres-Gonzalez, M, Gawlowski, T, Kocalis, H, Scott, BT & Dillmann, WH 2014 Mitochondrial 8-oxoguanine glycosylase decreases mitochondrial fragmentation and improves mitochondrial function in H9C2 cells under oxidative stress conditions. American Journal of Physiology-Cell Physiology 306 C221–C229 CrossRefGoogle ScholarPubMed
Tsai, H-H, Lee, W-R, Wang, P-H, Cheng, K-T, Chen, Y-C & Shen, S-C 2013 Propionibacterium acnes-induced iNOS and COX-2 protein expression via ROS-dependent NF-κB and AP-1 activation in macrophages. Journal of Dermatological Science 69 122–131 Google Scholar
Wang, X, Stavchansky, S, Zhao, B, Bynum, JA, Kerwin, SM & Bowman, PD 2008 Cytoprotection of human endothelial cells from menadione cytotoxicity by caffeic acid phenethyl ester: the role of heme oxygenase-1. European Journal of Pharmacology 591 28–35 Google Scholar
Wiegman, CH, Michaeloudes, C, Haji, G, Narang, P, Clarke, CJ, Russell, KE, Bao, W, Pavlidis, S, Barnes, PJ & Kanerva, J 2015 Oxidative stress–induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease. Journal of Allergy and Clinical Immunology 136 769–780 Google Scholar
Zha, L, Chen, J, Sun, S, Mao, L, Chu, X, Deng, H, Cai, J, Li, X, Liu, Z & Cao, W 2014 Soyasaponins can blunt inflammation by inhibiting the reactive oxygen species-mediated activation of PI3 K/Akt/NF-kB pathway. PLoS One 9 e107655 CrossRefGoogle Scholar
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