Peroxisome proliferator‑activated receptor γ prevents the production of NOD-like receptor family, pyrin domain containing 3 inflammasome and interleukin 1β in HK‑2 renal tubular epithelial cells stimulated by monosodium urate crystals

Hong,Wei; Hu,Shasha; Zou,Jianan; Xiao,Jing; Zhang,Xiaoli; Fu,Chensheng; Feng,Xinhui; Ye,Zhibin

doi:10.3892/mmr.2015.4145

Peroxisome proliferator‑activated receptor γ prevents the production of NOD-like receptor family, pyrin domain containing 3 inflammasome and interleukin 1β in HK‑2 renal tubular epithelial cells stimulated by monosodium urate crystals

Authors:
- Wei Hong
- Shasha Hu
- Jianan Zou
- Jing Xiao
- Xiaoli Zhang
- Chensheng Fu
- Xinhui Feng
- Zhibin Ye
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Affiliations: Department of Geriatrics, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China, Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, P.R. China
Published online on: July 29, 2015 https://doi.org/10.3892/mmr.2015.4145
Pages: 6221-6226

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Abstract

Recent evidence showed that peroxisome proliferator‑activated receptor γ (PPARγ) ameliorates a variety of inflammatory conditions. The present study aimed to investigate the role of PPARγ in regulating NOD-like receptor family, pyrin domain containing 3 (NALP3) inflammasome and interleukin (IL)‑1β levels during monosodium urate (MSU) crystal‑induced inflammation. HK‑2 cells were incubated with or without 200 µg/ml MSU crystals, and mRNA and protein levels of PPARγ were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. To verify the role of PPARγ, HK‑2 cells were pre‑treated with PPARγ agonist pioglitazone, and the levels of NALP3 inflammasome and IL‑1β were detected by western blot analysis and ELISA. The results showed that MSU crystals increased PPARγ expression in HK‑2 cells at 24 h, while the expression decreased to normal levels at 48 h. It was also demonstrated that although the PPARγ agonist pioglitazone did not alter the mRNA and protein levels of PPARγ, it significantly reduced the MSU crystal‑induced production of NALP3 inflammasome and IL‑1β in HK‑2 cells, possibly by increasing the level of PPARγ activity. In conclusion, the results of the present study indicated that PPARγ prevented NALP3 inflammasome formation and IL‑1β production in HK‑2 cells stimulated by MSU crystals, which indicated that PPARγ may represent a novel target for the treatment of hyperuricemic nephropathy.

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1	Zhu Y, Pandya BJ and Choi HK: Prevalence of gout and hyperuricemia in the US general population: The national health and nutrition examination survey 2007–2008. Arthritis Rheum. 63:3136–3141. 2011. View Article : Google Scholar : PubMed/NCBI
2	B L, T W, Hn Z, Ww Y, Hp Y, Cx L, J Y, Ry J and Hw N: The prevalence of hyperuricemia in China: A meta-analysis. BMC Public Health. 11:8322011. View Article : Google Scholar : PubMed/NCBI
3	Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K and Takishita S: Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 44:642–650. 2004. View Article : Google Scholar : PubMed/NCBI
4	Obermayr RP, Temml C, Gutjahr G, Knechtelsdorfer M, Oberbauer R and Klauser-Braun R: Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol. 19:2407–2413. 2008. View Article : Google Scholar : PubMed/NCBI
5	Khan SR: Crystal-induced inflammation of the kidneys: Results from human studies, animal models and tissue-culture studies. Clin Exp Nephrol. 8:75–88. 2004. View Article : Google Scholar : PubMed/NCBI
6	Akahoshi T, Murakami Y and Kitasato H: Recent advances in crystal-induced acute inflammation. Curr Opin Rheumatol. 19:146–150. 2007. View Article : Google Scholar : PubMed/NCBI
7	Maejima I, Takahashi A, Omori H, Kimura T, Takabatake Y, Saitoh T, Yamamoto A, Hamasaki M, Noda T, Isaka Y and Yoshimori T: Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. EMBO J. 32:2336–2347. 2013. View Article : Google Scholar : PubMed/NCBI
8	Shi Y, Evans JE and Rock KL: Molecular identification of a danger signal that alerts the immune system to dying cells. Nature. 425:516–521. 2003. View Article : Google Scholar : PubMed/NCBI
9	Martinon F, Pétrilli V, Mayor A, Tardivel A and Tschopp J: Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 440:237–241. 2006. View Article : Google Scholar : PubMed/NCBI
10	Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose-Girma M, Erickson S and Dixit VM: Differential activation of the inflammasome by caspase-1 adaptors ASC and Ipaf. Nature. 430:213–218. 2004. View Article : Google Scholar : PubMed/NCBI
11	Razmara M, Srinivasula SM, Wang L, Poyet JL, Geddes BJ, DiStefano PS, Bertin J and Alnemri ES: CARD-8 protein, a new CARD family member that regulates caspase-1 activation and apoptosis. J Biol Chem. 277:13952–13958. 2002. View Article : Google Scholar : PubMed/NCBI
12	Martinon F, Mayor A and Tschopp J: The inflammasomes: Guardians of the body. Annu Rev Immunol. 27:229–265. 2009. View Article : Google Scholar : PubMed/NCBI
13	Miao ZM, Zhao SH, Yan SL, Li CG, Wang YG, Meng DM, Zhou L and Mi QS: NALP3 inflammasome functional polymorphisms and gout susceptibility. Cell Cycle. 8:27–30. 2009. View Article : Google Scholar
14	Sims JE and Smith DE: The IL-1 family: Regulators of immunity. Nat Rev Immunol. 10:89–102. 2010. View Article : Google Scholar : PubMed/NCBI
15	Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S and Rock KL: MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest. 116:2262–2271. 2006. View Article : Google Scholar : PubMed/NCBI
16	So A, De Smedt T, Revaz S and Tschopp J: A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 9:R282007. View Article : Google Scholar : PubMed/NCBI
17	Kersten S, Desvergne B and Wahli W: Roles of PPARs in health and disease. Nature. 405:421–424. 2000. View Article : Google Scholar : PubMed/NCBI
18	Chana RS, Lewington AJ and Brunskill NJ: Differential effects of peroxisome proliferator activated receptor-gamma (PPAR gamma) ligands in proximal tubular cells: Thiazolidinediones are partial PPAR gamma agonists. Kidney Int. 65:2081–2090. 2004. View Article : Google Scholar : PubMed/NCBI
19	Ricote M, Li AC, Willson TM, Kelly CJ and Glass CK: The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature. 391:79–82. 1998. View Article : Google Scholar : PubMed/NCBI
20	Su CG, Wen X, Bailey ST, Jiang W, Rangwala SM, Keilbaugh SA, Flanigan A, Murthy S, Lazar MA and Wu GD: A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J Clin Invest. 104:383–389. 1999. View Article : Google Scholar : PubMed/NCBI
21	Matsuyama M, Yoshimura R, Hase T, Uchida J, Tsuchida K, Takemoto Y, Kawahito Y, Sano H and Nakatani T: Expression of peroxisome proliferator-activated receptor-gamma in renal ischemia-reperfusion injury. Transplant Proc. 37:1684–1685. 2005. View Article : Google Scholar : PubMed/NCBI
22	Ma LJ, Marcantoni C, Linton MF, Fazio S and Fogo AB: Peroxisome proliferator-activated receptor-gamma agonist troglitazone protects against nondiabetic glomerulosclerosis in rats. Kidney Int. 59:1899–1910. 2001. View Article : Google Scholar : PubMed/NCBI
23	Busso N and Ea HK: The mechanisms of inflammation in gout and pseudogout (CPP-induced arthritis). Reumatismo. 19:230–237. 2012.
24	Zou R, Xu G, Liu XC, Han M, Jiang JJ, Huang Q, He Y and Yao Y: PPARgamma agonists inhibit TGF-beta-PKA signaling in glomerulosclerosis. Acta Pharmacol Sin. 31:43–50. 2010. View Article : Google Scholar
25	Akahoshi T, Namai R, Murakami Y, Watanabe M, Matsui T, Nishimura A, Kitasato H, Kameya T and Kondo H: Rapid induction of peroxisome proliferator-activated receptor gamma expression in human monocytes by monosodium urate mono-hydrate crystals. Arthritis Rheum. 48:231–239. 2003. View Article : Google Scholar : PubMed/NCBI
26	Wang WM, Chen H, Zhong F, Lu Y, Han L and Chen N: Inhibitory effects of rosiglitazone on lipopolysaccharide-induced inflammation in a murine model and HK-2 cells. Am J Nephrol. 34:152–162. 2011. View Article : Google Scholar : PubMed/NCBI
27	Bhatt KH, Sodhi A and Chakraborty R: Peptidoglycan induced expression of peroxisome proliferator-activated receptor γ in mouse peritoneal macrophages: Role of ERK and JNK MAP kinases. Cytokine. 60:778–786. 2012. View Article : Google Scholar : PubMed/NCBI
28	Jiang C, Ting AT and Seed B: PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature. 391:82–86. 1998. View Article : Google Scholar : PubMed/NCBI
29	Tang SC, Chan LY, Leung JC, Cheng AS, Chan KW, Lan HY and Lai KN: Bradykinin and high glucose promote renal tubular inflammation. Nephrol Dial Transplant. 25:698–710. 2010. View Article : Google Scholar
30	Yang HC, Ma LJ, Ma J and Fogo AB: Peroxisome proliferator-activated receptor-gamma agonist is protective in podocyte injury-associated sclerosis. Kidney Int. 69:1756–1764. 2006. View Article : Google Scholar : PubMed/NCBI
31	Reel B, Guzeloglu M, Bagriyanik A, Atmaca S, Aykut K, Albayrak G and Hazan E: The effects of PPAR-γ agonist pioglitazone on renal ischemia/reperfusion injury in rats. J Surg Res. 182:176–184. 2013. View Article : Google Scholar
32	Taguchi K, Okada A, Yasui T, Kobayashi T, Ando R, Tozawa K and Kohri K: Pioglitazone, a peroxisome proliferator activated receptor γ agonist, decreases renal crystal deposition, oxidative stress and inflammation in hyperoxaluric rats. J Urol. 188:1002–1011. 2012. View Article : Google Scholar : PubMed/NCBI
33	Li X, Kimura H, Hirota K, Sugimoto H, Kimura N, Takahashi N, Fujii H and Yoshida H: Hypoxia reduces the expression and anti-inflammatory effects of peroxisome proliferator-activated receptor-gamma in human proximal renal tubular cells. Nephrol Dial Transplant. 22:1041–1051. 2007. View Article : Google Scholar : PubMed/NCBI
34	Ahn KO, Lim SW, Yang HJ, Li C, Sugawara A, Ito S, Choi BS, Kim YS, Kim J and Yang CW: Induction of PPAR gamma mRNA and protein expression by rosiglitazone in chronic cyclosporine nephropathy in the rat. Yonsei Med J. 48:308–316. 2007. View Article : Google Scholar : PubMed/NCBI
35	Matsuyama M, Yoshimura R, Kawahito Y, Sano H, Chargui J, Touraine JL and Nakatani T: Relationship between peroxisome proliferator-activated receptor-γ and renal ischemia-reperfusion injury. Mol Med Rep. 1:499–503. 2008.PubMed/NCBI