Supplemental Figures
Figure 1 (A, D-G) Quantitative analysis of the Western blot results. The
data are shown as the means ± SDs from 3 experiments. (B)
Immunofluorescence staining of iNOS (Alexa Fluor 594, red) and DAPI
nuclear staining in the kidney (200× magnification; scale bar 100 μm).
(C) IHC analysis of CD86 expression. (200× magnification; scale bar 100
μm).
Figure 2 (A-D) IHC analysis of CD86 expression. (200× magnification;
scale bar 100 μm). (E-F) Quantitative analysis of the Western blot
results. The data are shown as the means ± SDs from 3 experiments.
Figure 3 (A, B) Quantitative analysis of the Western blot results. The
data are shown as the means ± SDs from 3 experiments.
Figure 4 (A-C) Quantitative analysis of the Western blot results. The
data are shown as the means ± SDs from 3 experiments.
Figure 5 (A-C) Quantitative analysis of the Western blot results. The
data are shown as the means ± SDs from 3 experiments.
Agostini, L., F. Martinon, K. Burns, M. F. McDermott, P. N. Hawkins and
J. Tschopp (2004). ”NALP3 forms an IL-1beta-processing inflammasome with
increased activity in Muckle-Wells autoinflammatory disorder.”Immunity 20 (3):
319-325https://doi.org/10.1016/s1074-7613(04)00046-9 .
Anders, H. J. and M. Ryu (2011). ”Renal microenvironments and macrophage
phenotypes determine progression or resolution of renal inflammation and
fibrosis.” Kidney Int 80 (9):
915-925https://doi.org/10.1038/ki.2011.217 .
Baek, K. J., S. Ji, Y. C. Kim and Y. Choi (2015). ”Association of the
invasion ability of Porphyromonas gingivalis with the severity of
periodontitis.” Virulence 6 (3):
274-281https://doi.org/10.1080/21505594.2014.1000764 .
Bao, H. and A. Peng (2016). ”The Green Tea
Polyphenol(-)-epigallocatechin-3-gallate and its beneficial roles in
chronic kidney disease.” J Transl Int Med 4 (3):
99-103https://doi.org/10.1515/jtim-2016-0031 .
Bhargava, S., E. Merckelbach, H. Noels, A. Vohra and J. Jankowski
(2022). ”Homeostasis in the Gut Microbiota in Chronic Kidney Disease.”Toxins (Basel)14 (10)https://doi.org/10.3390/toxins14100648 .
Bui, F. Q., C. L. C. Almeida-da-Silva, B. Huynh, A. Trinh, J. Liu, J.
Woodward, H. Asadi, . . . D. M. Ojcius (2019). ”Association between
periodontal pathogens and systemic disease.” Biomed J42 (1): 27-35https://doi.org/10.1016/j.bj.2018.12.001 .
Coresh, J., E. Selvin, L. A. Stevens, J. Manzi, J. W. Kusek, P. Eggers,
F. Van Lente, . . . A. S. Levey (2007). ”Prevalence of chronic kidney
disease in the United States.” JAMA 298 (17):
2038-2047https://doi.org/10.1001/jama.298.17.2038 .
D’Aiuto, F., M. Parkar, G. Andreou, J. Suvan, P. M. Brett, D. Ready and
M. S. Tonetti (2004). ”Periodontitis and systemic inflammation: control
of the local infection is associated with a reduction in serum
inflammatory markers.” J Dent Res 83 (2):
156-160https://doi.org/10.1177/154405910408300214 .
Deschamps-Lenhardt, S., R. Martin-Cabezas, T. Hannedouche and O. Huck
(2019). ”Association between periodontitis and chronic kidney disease:
Systematic review and meta-analysis.” Oral Dis 25 (2):
385-402https://doi.org/10.1111/odi.12834 .
Dixon, S. J., K. M. Lemberg, M. R. Lamprecht, R. Skouta, E. M. Zaitsev,
C. E. Gleason, D. N. Patel, . . . B. R. Stockwell (2012). ”Ferroptosis:
an iron-dependent form of nonapoptotic cell death.” Cell149 (5):
1060-1072https://doi.org/10.1016/j.cell.2012.03.042 .
Fang, F., B. Wu, Q. Qu, J. Gao, W. Yan, X. Huang, D. Ma, . . . Y. Liu
(2015). ”The clinical response and systemic effects of non-surgical
periodontal therapy in end-stage renal disease patients: a 6-month
randomized controlled clinical trial.” J Clin Periodontol42 (6): 537-546https://doi.org/10.1111/jcpe.12411 .
Fisher, M. A., G. W. Taylor, P. N. Papapanou, M. Rahman and S. M.
Debanne (2008). ”Clinical and serologic markers of periodontal infection
and chronic kidney disease.” J Periodontol 79 (9):
1670-1678https://doi.org/10.1902/jop.2008.070569 .
Genco, R. J. and W. S. Borgnakke (2013). ”Risk factors for periodontal
disease.” Periodontol 2000 62 (1):
59-94https://doi.org/10.1111/j.1600-0757.2012.00457.x .
Giuliani, K. T. K., A. Grivei, P. Nag, X. Wang, M. Rist, K. Kildey, B.
Law, . . . A. J. Kassianos (2022). ”Hypoxic human proximal tubular
epithelial cells undergo ferroptosis and elicit an NLRP3 inflammasome
response in CD1c(+) dendritic cells.” Cell Death Dis13 (8): 739https://doi.org/10.1038/s41419-022-05191-z .
Goncalves, A. C., L. S. Ferreira, F. A. Manente, C. de Faria, M. C.
Polesi, C. R. de Andrade, D. S. Zamboni, . . . I. Z. Carlos (2017). ”The
NLRP3 inflammasome contributes to host protection during Sporothrix
schenckii infection.” Immunology 151 (2):
154-166https://doi.org/10.1111/imm.12719 .
Holden, J. A., T. J. Attard, K. M. Laughton, A. Mansell, N. M.
O’Brien-Simpson and E. C. Reynolds (2014). ”Porphyromonas gingivalis
lipopolysaccharide weakly activates M1 and M2 polarized mouse
macrophages but induces inflammatory cytokines.” Infect Immun82 (10): 4190-4203https://doi.org/10.1128/IAI.02325-14 .
Huang, Y., C. Tian, Q. Li and Q. Xu (2019). ”TET1 Knockdown Inhibits
Porphyromonas gingivalis LPS/IFN-gamma-Induced M1 Macrophage
Polarization through the NF-kappaB Pathway in THP-1 Cells.” Int J
Mol Sci 20 (8)https://doi.org/10.3390/ijms20082023 .
Iwasaki, M., G. W. Taylor, M. C. Manz, N. Kaneko, S. Imai, A. Yoshihara
and H. Miyazaki (2012). ”Serum antibody to Porphyromonas gingivalis in
chronic kidney disease.” J Dent Res 91 (9):
828-833https://doi.org/10.1177/0022034512455063 .
Jha, V., G. Garcia-Garcia, K. Iseki, Z. Li, S. Naicker, B. Plattner, R.
Saran, . . . C. W. Yang (2013). ”Chronic kidney disease: global
dimension and perspectives.” Lancet 382 (9888):
260-272https://doi.org/10.1016/S0140-6736(13)60687-X .
Jiao, J., W. Jing, Y. Si, X. Feng, B. Tai, D. Hu, H. Lin, . . . X. Wang
(2021). ”The prevalence and severity of periodontal disease in Mainland
China: Data from the Fourth National Oral Health Survey (2015-2016).”J Clin Periodontol 48 (2):
168-179https://doi.org/10.1111/jcpe.13396 .
Jomen, W., T. Ohtake, T. Akita, D. Suto, H. Yagi, Y. Osawa and Y. Kohgo
(2022). ”Iron chelator deferasirox inhibits NF-kappaB activity in
hepatoma cells and changes sorafenib-induced programmed cell deaths.”Biomed Pharmacother 153 :
113363https://doi.org/10.1016/j.biopha.2022.113363 .
Kapellas, K., A. Singh, M. Bertotti, G. G. Nascimento, L. M. Jamieson
and C. K. D. c. Perio (2019). ”Periodontal and chronic kidney disease
association: A systematic review and meta-analysis.” Nephrology
(Carlton) 24 (2):
202-212https://doi.org/10.1111/nep.13225 .
Kassebaum, N. J., E. Bernabe, M. Dahiya, B. Bhandari, C. J. Murray and
W. Marcenes (2014). ”Global burden of severe periodontitis in 1990-2010:
a systematic review and meta-regression.” J Dent Res93 (11):
1045-1053https://doi.org/10.1177/0022034514552491 .
Kon, V., M. F. Linton and S. Fazio (2011). ”Atherosclerosis in chronic
kidney disease: the role of macrophages.” Nat Rev Nephrol7 (1): 45-54https://doi.org/10.1038/nrneph.2010.157 .
Kretz-Remy, C., P. Mehlen, M. E. Mirault and A. P. Arrigo (1996).
”Inhibition of I kappa B-alpha phosphorylation and degradation and
subsequent NF-kappa B activation by glutathione peroxidase
overexpression.” J Cell Biol 133 (5):
1083-1093https://doi.org/10.1083/jcb.133.5.1083 .
Lam, R. S., N. M. O’Brien-Simpson, J. A. Holden, J. C. Lenzo, S. B. Fong
and E. C. Reynolds (2016). ”Unprimed, M1 and M2 Macrophages
Differentially Interact with Porphyromonas gingivalis.” PLoS One11 (7):
e0158629https://doi.org/10.1371/journal.pone.0158629 .
Lech, M., R. Grobmayr, M. Ryu, G. Lorenz, I. Hartter, S. R. Mulay, H. E.
Susanti, . . . H. J. Anders (2014). ”Macrophage phenotype controls
long-term AKI outcomes–kidney regeneration versus atrophy.” J
Am Soc Nephrol 25 (2):
292-304https://doi.org/10.1681/ASN.2013020152 .
Lew, J. H., K. Naruishi, Y. Kajiura, Y. Nishikawa, T. Ikuta, J. I. Kido
and T. Nagata (2018). ”High Glucose-Mediated Cytokine Regulation in
Gingival Fibroblasts and THP-1 Macrophage: a Possible Mechanism of
Severe Periodontitis with Diabetes.” Cell Physiol Biochem50 (3): 973-986https://doi.org/10.1159/000494481 .
Li, C., X. Y. Ding, D. M. Xiang, J. Xu, X. L. Huang, F. F. Hou and Q. G.
Zhou (2015). ”Enhanced M1 and Impaired M2 Macrophage Polarization and
Reduced Mitochondrial Biogenesis via Inhibition of AMP Kinase in Chronic
Kidney Disease.” Cell Physiol Biochem 36 (1):
358-372https://doi.org/10.1159/000430106 .
Liu, L., H. Guo, A. Song, J. Huang, Y. Zhang, S. Jin, S. Li, . . . P.
Yang (2020). ”Progranulin inhibits LPS-induced macrophage M1
polarization via NF-small ka, CyrillicB and MAPK pathways.” BMC
Immunol 21 (1):
32https://doi.org/10.1186/s12865-020-00355-y .
Lv, J. C. and L. X. Zhang (2019). ”Prevalence and Disease Burden of
Chronic Kidney Disease.” Adv Exp Med Biol 1165 :
3-15https://doi.org/10.1007/978-981-13-8871-2_1 .
Lv, X., C. Fan, Z. Jiang, W. Wang, X. Qiu and Q. Ji (2021).
”Isoliquiritigenin alleviates P. gingivalis-LPS/ATP-induced pyroptosis
by inhibiting NF-kappaB/ NLRP3/GSDMD signals in human gingival
fibroblasts.” Int Immunopharmacol 101 (Pt B):
108338https://doi.org/10.1016/j.intimp.2021.108338 .
Mahendra, J., P. Palathingal, L. Mahendra, K. J. Alzahrani, H. J.
Banjer, K. F. Alsharif, I. F. Halawani, . . . S. Patil (2022). ”Impact
of Red Complex Bacteria and TNF-alpha Levels on the Diabetic and Renal
Status of Chronic Kidney Disease Patients in the Presence and Absence of
Periodontitis.” Biology (Basel)11 (3)https://doi.org/10.3390/biology11030451 .
Mussbacher, M., M. Salzmann, C. Brostjan, B. Hoesel, C. Schoergenhofer,
H. Datler, P. Hohensinner, . . . J. A. Schmid (2019). ”Cell
Type-Specific Roles of NF-kappaB Linking Inflammation and Thrombosis.”Front Immunol 10 :
85https://doi.org/10.3389/fimmu.2019.00085 .
Navarrete, M., J. Garcia, N. Dutzan, L. Henriquez, J. Puente, P.
Carvajal, M. Hernandez, . . . J. Gamonal (2014). ”Interferon-gamma,
interleukins-6 and -4, and factor XIII-A as indirect markers of the
classical and alternative macrophage activation pathways in chronic
periodontitis.” J Periodontol 85 (5):
751-760https://doi.org/10.1902/jop.2013.130078 .
Palm, E., I. Demirel, T. Bengtsson and H. Khalaf (2015). ”The role of
toll-like and protease-activated receptors in the expression of
cytokines by gingival fibroblasts stimulated with the periodontal
pathogen Porphyromonas gingivalis.” Cytokine 76 (2):
424-432https://doi.org/10.1016/j.cyto.2015.08.263 .
Pang, Q., P. Wang, Y. Pan, X. Dong, T. Zhou, X. Song and A. Zhang
(2022). ”Irisin protects against vascular calcification by activating
autophagy and inhibiting NLRP3-mediated vascular smooth muscle cell
pyroptosis in chronic kidney disease.” Cell Death Dis13 (3): 283https://doi.org/10.1038/s41419-022-04735-7 .
Parsegian, K., D. Randall, M. Curtis and E. Ioannidou (2022).
”Association between periodontitis and chronic kidney disease.”Periodontol 2000 89 (1):
114-124https://doi.org/10.1111/prd.12431 .
Qiao, S., B. Li, Q. Cai, Z. Li, Z. Yin, J. He, Y. Li, . . . W. Meng
(2022). ”Involvement of ferroptosis in Porphyromonas gingivalis
lipopolysaccharide-stimulated periodontitis in vitro and in vivo.”Oral Dishttps://doi.org/10.1111/odi.14292 .
Rehnqvist, N. (1981). ”Clinical experience with intravenous metoprolol
in supraventricular tachyarrhythmias. A multicentre study.” Ann
Clin Res 13 Suppl 30 : 68-72
Ricardo, S. D., H. van Goor and A. A. Eddy (2008). ”Macrophage diversity
in renal injury and repair.” J Clin Invest 118 (11):
3522-3530https://doi.org/10.1172/JCI36150 .
Sharma, P., T. Dietrich, A. Sidhu, V. Vithlani, M. Rahman, S. Stringer,
M. Jesky, . . . I. L. Chapple (2014). ”The periodontal health component
of the Renal Impairment In Secondary Care (RIISC) cohort study: a
description of the rationale, methodology and initial baseline results.”J Clin Periodontol 41 (7):
653-661https://doi.org/10.1111/jcpe.12263 .
Siribamrungwong, M., K. Yothasamutr and K. Puangpanngam (2014).
”Periodontal treatment reduces chronic systemic inflammation in
peritoneal dialysis patients.” Ther Apher Dial 18 (3):
305-308https://doi.org/10.1111/1744-9987.12105 .
Sucajtys-Szulc, E., A. Debska-Slizien, B. Rutkowski, M. Szolkiewicz, J.
Swierczynski and R. T. Smolenski (2022). ”Hepatocyte Nuclear Factor
1alpha Proinflammatory Effect Linked to the Overexpression of Liver
Nuclear Factor-kappaB in Experimental Model of Chronic Kidney Disease.”Int J Mol Sci23 (16)https://doi.org/10.3390/ijms23168883 .
Sun, X., J. Gao, X. Meng, X. Lu, L. Zhang and R. Chen (2021). ”Polarized
Macrophages in Periodontitis: Characteristics, Function, and Molecular
Signaling.” Front Immunol 12 :
763334https://doi.org/10.3389/fimmu.2021.763334 .
Tonetti, M. S., T. E. Van Dyke and E. F. P. A. A. P. w. Working group 1
of the joint (2013). ”Periodontitis and atherosclerotic cardiovascular
disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis
and Systemic Diseases.” J Clin Periodontol 40 Suppl 14 :
S24-29https://doi.org/10.1111/jcpe.12089 .
Vilela, E. M., J. A. Bastos, N. Fernandes, A. P. Ferreira, A. Chaoubah
and M. G. Bastos (2011). ”Treatment of chronic periodontitis decreases
serum prohepcidin levels in patients with chronic kidney disease.”Clinics (Sao Paulo) 66 (4):
657-662https://doi.org/10.1590/s1807-59322011000400022 .
Wang, J., Y. Liu, Y. Wang and L. Sun (2021). ”The Cross-Link between
Ferroptosis and Kidney Diseases.” Oxid Med Cell Longev2021 : 6654887https://doi.org/10.1155/2021/6654887 .
Wang, L., X. Xu, M. Zhang, C. Hu, X. Zhang, C. Li, S. Nie, . . . M. Zhou
(2023). ”Prevalence of Chronic Kidney Disease in China: Results From the
Sixth China Chronic Disease and Risk Factor Surveillance.” JAMA
Intern Med 183 (4):
298-310https://doi.org/10.1001/jamainternmed.2022.6817 .
Wang, Y., C. Li, Y. Wan, M. Qi, Q. Chen, Y. Sun, X. Sun, . . . L. Wang
(2021). ”Quercetin-Loaded Ceria Nanocomposite Potentiate
Dual-Directional Immunoregulation via Macrophage Polarization against
Periodontal Inflammation.” Small 17 (41):
e2101505https://doi.org/10.1002/smll.202101505 .
Wang, Y. J., Y. Y. Chen, C. M. Hsiao, M. H. Pan, B. J. Wang, Y. C. Chen,
C. T. Ho, . . . R. J. Chen (2020). ”Induction of Autophagy by
Pterostilbene Contributes to the Prevention of Renal Fibrosis via
Attenuating NLRP3 Inflammasome Activation and Epithelial-Mesenchymal
Transition.” Front Cell Dev Biol 8 :
436https://doi.org/10.3389/fcell.2020.00436 .
Wen, Y., X. Lu, J. Ren, J. R. Privratsky, B. Yang, N. P. Rudemiller, J.
Zhang, . . . S. D. Crowley (2019). ”KLF4 in Macrophages Attenuates
TNFalpha-Mediated Kidney Injury and Fibrosis.” J Am Soc Nephrol30 (10): 1925-1938https://doi.org/10.1681/ASN.2019020111 .
Xiao, Z., B. Kong, J. Fang, T. Qin, C. Dai, W. Shuai and H. Huang
(2021). ”Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac
dysfunction.” Bioengineered 12 (2):
9367-9376https://doi.org/10.1080/21655979.2021.2001913 .
Xu, M., J. Tao, Y. Yang, S. Tan, H. Liu, J. Jiang, F. Zheng, . . . B. Wu
(2020). ”Ferroptosis involves in intestinal epithelial cell death in
ulcerative colitis.” Cell Death Dis 11 (2):
86https://doi.org/10.1038/s41419-020-2299-1 .
Yang, J., Y. Zhu, D. Duan, P. Wang, Y. Xin, L. Bai, Y. Liu, . . . Y. Xu
(2018). ”Enhanced activity of macrophage M1/M2 phenotypes in
periodontitis.” Arch Oral Biol 96 :
234-242https://doi.org/10.1016/j.archoralbio.2017.03.006 .
Yao, C., D. Lan, X. Li, Y. Wang and S. Qi (2023). ”Porphyromonas
gingivalis triggers inflammation in hepatocyte depend on ferroptosis via
activating the NF-kappaB signaling pathway.” Oral
Dishttps://doi.org/10.1111/odi.14537 .
Yao, C., D. Lan, X. Li, Y. Wang, S. Qi and Y. Liu (2023). ”Porphyromonas
gingivalis is a risk factor for the development of nonalcoholic fatty
liver disease via ferroptosis.” Microbes Infect 25 (1-2):
105040https://doi.org/10.1016/j.micinf.2022.105040 .
Ye, Y., A. Chen, L. Li, Q. Liang, S. Wang, Q. Dong, M. Fu, . . . J. Yan
(2022). ”Repression of the antiporter SLC7A11/glutathione/glutathione
peroxidase 4 axis drives ferroptosis of vascular smooth muscle cells to
facilitate vascular calcification.” Kidney Int 102 (6):
1259-1275https://doi.org/10.1016/j.kint.2022.07.034 .
Zhou, L., X. Xue, Q. Hou and C. Dai (2022). ”Targeting Ferroptosis
Attenuates Interstitial Inflammation and Kidney Fibrosis.” Kidney
Dis (Basel) 8 (1):
57-71https://doi.org/10.1159/000517723 .