Top

Published in:

01-03-2018 | ORIGINAL ARTICLE

Protein Disulfide Isomerase Silence Inhibits Inflammatory Functions of Macrophages by Suppressing Reactive Oxygen Species and NF-κB Pathway

Authors: Yinbo Xiao, Chaohong Li, Minghui Gu, Haixing Wang, Weishen Chen, Guotian Luo, Guangpu Yang, Ziji Zhang, Yangchun Zhang, Guoyan Xian, Ziqing Li, Puyi Sheng

Published in: Inflammation | Issue 2/2018

Abstract

Macrophages play an essential role in inflammation. Protein disulfide isomerase (PDI) is central to the redox system, which is closely linked with the inflammatory function of macrophages. However, the relationship between PDI and inflammation is still unknown. In this study, we tested the effects of PDI on inflammatory responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). Using CRISPR/Cas9 system, we found that PDI knockout suppressed migration, M1 polarization, and secretion of tumor necrosis factor-α (TNF-α) and interluekin-6 (IL-6). The repression of these inflammatory processes was accompanied by decreased production of reactive oxygen species (ROS). PDI ablation also inactivated the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activated the phosphorylation of NF-κB inhibitor alpha (IκBα). These findings demonstrate that PDI knockout inhibits the inflammatory function of macrophages by decreasing ROS production and inactivating NF-κB pathway.

Kapadia, Bhaveen H., Richard A. Berg, Jacqueline A. Daley, Jan Fritz, Anil Bhave, and Michael A. Mont. 2016. Periprosthetic joint infection. The Lancet 387 (10016): 386–394. https://doi.org/10.1016/s0140-6736(14)61798-0.CrossRef

Smolen, J.S., D. Aletaha, and I.B. McInnes. 2016. Rheumatoid arthritis. Lancet. https://doi.org/10.1016/S0140-6736(16)30173-8.

Franken, L., M. Schiwon, and C. Kurts. 2016. Macrophages: Sentinels and regulators of the immune system. Cellular Microbiology 18 (4): 475–487. https://doi.org/10.1111/cmi.12580.CrossRefPubMed

Soehnlein, O., S. Steffens, A. Hidalgo, and C. Weber. 2017. Neutrophils as protagonists and targets in chronic inflammation. Nature Reviews. Immunology 17 (4): 248–261. https://doi.org/10.1038/nri.2017.10.CrossRefPubMed

Mallat, Z. 2014. Macrophages. Arteriosclerosis, Thrombosis, and Vascular Biology 34 (12): 2509–2519. https://doi.org/10.1161/ATVBAHA.114.304794.CrossRefPubMed

Lavin, Y., A. Mortha, A. Rahman, and M. Merad. 2015. Regulation of macrophage development and function in peripheral tissues. Nature Reviews. Immunology 15 (12): 731–744. https://doi.org/10.1038/nri3920.CrossRefPubMedPubMedCentral

Weiss, G., and U.E. Schaible. 2015. Macrophage defense mechanisms against intracellular bacteria. Immunological Reviews 264 (1): 182–203. https://doi.org/10.1111/imr.12266.CrossRefPubMedPubMedCentral

Bashir, S., Y. Sharma, A. Elahi, and F. Khan. 2015. Macrophage polarization: the link between inflammation and related diseases. Inflammation Research. https://doi.org/10.1007/s00011-015-0874-1.

Murray, P.J., J.E. Allen, S.K. Biswas, E.A. Fisher, D.W. Gilroy, S. Goerdt, S. Gordon, et al. 2014. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41 (1): 14–20. https://doi.org/10.1016/j.immuni.2014.06.008.CrossRefPubMedPubMedCentral

10.

Sica, A., M. Erreni, P. Allavena, and C. Porta. 2015. Macrophage polarization in pathology. Cellular and Molecular Life Sciences 72 (21): 4111–4126. https://doi.org/10.1007/s00018-015-1995-y.CrossRefPubMed

11.

Antonios, J.K., Z. Yao, C. Li, A.J. Rao, and S.B. Goodman. 2013. Macrophage polarization in response to wear particles in vitro. Cellular & Molecular Immunology 10 (6): 471–482. https://doi.org/10.1038/cmi.2013.39.CrossRef

12.

Vasconcelos, D.P., M. Costa, I.F. Amaral, M.A. Barbosa, A.P. Aguas, and J.N. Barbosa. 2015. Modulation of the inflammatory response to chitosan through M2 macrophage polarization using pro-resolution mediators. Biomaterials 37: 116–123. https://doi.org/10.1016/j.biomaterials.2014.10.035.CrossRefPubMed

13.

Chen, Weishen, Ziqing Li, Ying Guo, Yuhuan Zhou, Yangchun Zhang, Guotian Luo, Xing Yang, Chaohong Li, Weiming Liao, and Puyi Sheng. 2015. Wear particles impair antimicrobial activity via suppression of reactive oxygen species generation and ERK1/2 phosphorylation in activated macrophages. Inflammation 38 (3): 1289–1296. https://doi.org/10.1007/s10753-014-0099-4.CrossRefPubMed

14.

Chen, Weishen, Ziqing Li, Ying Guo, Yuhuan Zhou, Ziji Zhang, Yangchun Zhang, Guotian Luo, et al. 2015. Wear particles promote reactive oxygen species-mediated inflammation via the nicotinamide adenine dinucleotide phosphate oxidase pathway in macrophages surrounding loosened implants. Cellular Physiology and Biochemistry 35 (5): 1857–1867. https://doi.org/10.1159/000373996.CrossRefPubMed

15.

Lei, Y., K. Wang, L. Deng, Y. Chen, E.C. Nice, and C. Huang. 2015. Redox regulation of inflammation: old elements, a new story. Medicinal Research Reviews 35 (2): 306–340. https://doi.org/10.1002/med.21330.CrossRefPubMed

16.

Luo, G., Z. Li, Y. Wang, H. Wang, Z. Zhang, W. Chen, Y. Zhang, et al. 2016. Resveratrol protects against titanium particle-induced aseptic loosening through reduction of oxidative stress and inactivation of NF-kappaB. Inflammation. https://doi.org/10.1007/s10753-016-0306-6.

17.

Morgan, M.J., and Z.G. Liu. 2011. Crosstalk of reactive oxygen species and NF-kappaB signaling. Cell Research 21 (1): 103–115. https://doi.org/10.1038/cr.2010.178.CrossRefPubMed

18.

Zhou, G., S. Meng, Y. Li, Y.T. Ghebre, and J.P. Cooke. 2016. Optimal ROS signaling is critical for nuclear reprogramming. Cell Reports 15 (5): 919–925. https://doi.org/10.1016/j.celrep.2016.03.084.CrossRefPubMedPubMedCentral

19.

Ezraty, B., A. Gennaris, F. Barras, and J.F. Collet. 2017. Oxidative stress, protein damage and repair in bacteria. Nature Reviews Microbiology 15 (7): 385–396. https://doi.org/10.1038/nrmicro.2017.26.CrossRefPubMed

20.

Sies, H., C. Berndt, and D.P. Jones. 2017. Oxidative stress. Annual Review of Biochemistry 86: 715–748. https://doi.org/10.1146/annurev-biochem-061516-045037.CrossRefPubMed

21.

Zhang, J., X. Wang, V. Vikash, Q. Ye, D. Wu, Y. Liu, and W. Dong. 2016. ROS and ROS-mediated cellular signaling. Oxidative Medicine and Cellular Longevity 2016: 4350965. https://doi.org/10.1155/2016/4350965.PubMedPubMedCentral

22.

Blaser, H., C. Dostert, T.W. Mak, and D. Brenner. 2016. TNF and ROS crosstalk in inflammation. Trends in Cell Biology. https://doi.org/10.1016/j.tcb.2015.12.002.

23.

Hayden, M.S., and S. Ghosh. 2004. Signaling to NF-kappaB. Genes & Development 18 (18): 2195–2224. https://doi.org/10.1101/gad.1228704.CrossRef

24.

Sharif, O., V.N. Bolshakov, S. Raines, P. Newham, and N.D. Perkins. 2007. Transcriptional profiling of the LPS induced NF-kappaB response in macrophages. BMC Immunology 8: 1. https://doi.org/10.1186/1471-2172-8-1.CrossRefPubMedPubMedCentral

25.

Ping, S., S. Liu, Y. Zhou, Z. Li, Y. Li, K. Liu, A.S. Bardeesi, et al. 2017. Protein disulfide isomerase-mediated apoptosis and proliferation of vascular smooth muscle cells induced by mechanical stress and advanced glycosylation end products result in diabetic mouse vein graft atherosclerosis. Cell Death & Disease 8 (5): e2818. https://doi.org/10.1038/cddis.2017.213.CrossRef

26.

Wang, L., X. Wang, and C.C. Wang. 2015. Protein disulfide-isomerase, a folding catalyst and a redox-regulated chaperone. Free Radical Biology and Medicine 83: 305–313. https://doi.org/10.1016/j.freeradbiomed.2015.02.007.CrossRefPubMed

27.

Cho, J. 2013. Protein disulfide isomerase in thrombosis and vascular inflammation. Journal of Thrombosis and Haemostasis 11 (12): 2084–2091. https://doi.org/10.1111/jth.12413.CrossRefPubMedPubMedCentral

28.

Benham, A.M. 2012. The protein disulfide isomerase family: key players in health and disease. Antioxidants & Redox Signaling 16 (8): 781–789. https://doi.org/10.1089/ars.2011.4439.CrossRef

29.

Yoshioka, J. 2015. Thioredoxin superfamily and its effects on cardiac physiology and pathology. Comprehensive Physiology 5 (2): 513–530. https://doi.org/10.1002/cphy.c140042.CrossRefPubMed

30.

Brychtova, V., A. Mohtar, B. Vojtesek, and T.R. Hupp. 2015. Mechanisms of anterior gradient-2 regulation and function in cancer. Seminars in Cancer Biology 33: 16–24. https://doi.org/10.1016/j.semcancer.2015.04.005.CrossRefPubMed

31.

Hahm, E., J. Li, K. Kim, S. Huh, S. Rogelj, and J. Cho. 2013. Extracellular protein disulfide isomerase regulates ligand-binding activity of alphaMbeta2 integrin and neutrophil recruitment during vascular inflammation. Blood 121 (19):3789–3800, S3781-3715. doi:https://doi.org/10.1182/blood-2012-11-467985.

32.

Higuchi, T., Y. Watanabe, and I. Waga. 2004. Protein disulfide isomerase suppresses the transcriptional activity of NF-kappaB. Biochemical and Biophysical Research Communications 318 (1): 46–52. https://doi.org/10.1016/j.bbrc.2004.04.002.CrossRefPubMed

33.

Ran, F.A., P.D. Hsu, J. Wright, V. Agarwala, D.A. Scott, and F. Zhang. 2013. Genome engineering using the CRISPR-Cas9 system. Nature Protocols 8 (11): 2281–2308. https://doi.org/10.1038/nprot.2013.143.CrossRefPubMedPubMedCentral

34.

Li, Z., C. Li, Y. Zhou, W. Chen, G. Luo, Z. Zhang, H. Wang, Y. Zhang, D. Xu, and P. Sheng. 2016. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells. American Journal of Physiology. Endocrinology and Metabolism 310 (5): E355–E366. https://doi.org/10.1152/ajpendo.00309.2015.CrossRefPubMed

35.

Trujillo, M., L. Folkes, S. Bartesaghi, B. Kalyanaraman, P. Wardman, and R. Radi. 2005. Peroxynitrite-derived carbonate and nitrogen dioxide radicals readily react with lipoic and dihydrolipoic acid. Free Radical Biology & Medicine 39 (2): 279–288. https://doi.org/10.1016/j.freeradbiomed.2005.03.014.CrossRef

36.

Wrona, M., and P. Wardman. 2006. Properties of the radical intermediate obtained on oxidation of 2′,7′-dichlorodihydrofluorescein, a probe for oxidative stress. Free Radical Biology & Medicine 41 (4): 657–667. https://doi.org/10.1016/j.freeradbiomed.2006.05.006.CrossRef

37.

West, A.P., I.E. Brodsky, C. Rahner, D.K. Woo, H. Erdjument-Bromage, P. Tempst, M.C. Walsh, Y. Choi, G.S. Shadel, and S. Ghosh. 2011. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472 (7344): 476–480. https://doi.org/10.1038/nature09973.CrossRefPubMedPubMedCentral

38.

Camejo, D., A. Guzman-Cedeno, and A. Moreno. 2016. Reactive oxygen species, essential molecules, during plant-pathogen interactions. Plant Physiology and Biochemistry 103: 10–23. https://doi.org/10.1016/j.plaphy.2016.02.035.CrossRefPubMed

39.

Cash, T.P., Y. Pan, and M.C. Simon. 2007. Reactive oxygen species and cellular oxygen sensing. Free Radical Biology & Medicine 43 (9): 1219–1225. https://doi.org/10.1016/j.freeradbiomed.2007.07.001.CrossRef

40.

Laurindo, F.R.M., L.A. Pescatore, and D.D. Fernandes. 2012. Protein disulfide isomerase in redox cell signaling and homeostasis. Free Radical Biology and Medicine 52 (9): 1954–1969. https://doi.org/10.1016/j.freeradbiomed.2012.02.037.CrossRefPubMed

41.

Edman, J.C., L. Ellis, R.W. Blacher, R.A. Roth, and W.J. Rutter. 1985. Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin. Nature 317 (6034): 267–270.CrossRefPubMed

42.

Laboissiere, M.C., S.L. Sturley, and R.T. Raines. 1995. The essential function of protein-disulfide isomerase is to unscramble non-native disulfide bonds. The Journal of Biological Chemistry 270 (47): 28006–28009.CrossRefPubMed

43.

Ryo, A., F. Suizu, Y. Yoshida, K. Perrem, Y.C. Liou, G. Wulf, R. Rottapel, S. Yamaoka, and K.P. Lu. 2003. Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65/RelA. Molecular Cell 12 (6): 1413–1426.CrossRefPubMed

Title: Protein Disulfide Isomerase Silence Inhibits Inflammatory Functions of Macrophages by Suppressing Reactive Oxygen Species and NF-κB Pathway
Authors: Yinbo Xiao
Chaohong Li
Minghui Gu
Haixing Wang
Weishen Chen
Guotian Luo
Guangpu Yang
Ziji Zhang
Yangchun Zhang
Guoyan Xian
Ziqing Li
Puyi Sheng
Publication date: 01-03-2018
Publisher: Springer US
Published in: Inflammation / Issue 2/2018
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-017-0717-z

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Protein Disulfide Isomerase Silence Inhibits Inflammatory Functions of Macrophages by Suppressing Reactive Oxygen Species and NF-κB Pathway

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2018

Deficiency of IL-18 Aggravates Esophageal Carcinoma Through Inhibiting IFN-γ Production by CD8+T Cells and NK Cells

α7-nAChR Activation Has an Opposite Effect on Healing of Covered and Uncovered Wounds

Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Lipopolysaccharide (LPS)-Induced Inflammatory Responses in Primary Human Osteoarthritic Fibroblast-Like Synoviocytes

Bone Marrow Mesenchymal Stem Cells Combat Lipopolysaccharide-Induced Sepsis in Rats via Amendment of P38-MAPK Signaling Cascade

Umbelliferone Alleviates Myocardial Ischemia: the Role of Inflammation and Apoptosis

Anti-inflammatory Effects of Rosmarinic Acid in Lipopolysaccharide-Induced Mastitis in Mice

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page