Autoimmune regulator regulates autophagy in THP-1 human monocytes

Liang SHI, Li-Hua HU, Yi-Rong LI

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PDF(231 KB)
Front. Med. ›› 2010, Vol. 4 ›› Issue (3) : 336-341. DOI: 10.1007/s11684-010-0096-4
RESEARCH ARTICLE
RESEARCH ARTICLE

Autoimmune regulator regulates autophagy in THP-1 human monocytes

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Abstract

The autoimmune regulator (AIRE) is a crucial factor for the induction of central tolerance, and mutations in this gene lead to abnormal immune responses. However, the role of AIRE in autophagy in immune cells, especially in monocytes, is obscure. In the present study, we found that overexpression of AIRE in THP-1 human monocytes resulted in increased endogenous light chain 3 (LC3)-II level and elevated LC3 positive vesicles. Moreover, an autophagy inhibitor or knockdown of AIRE by small interference RNA attenuated these effects. In contrast, the expression of p62/SQSTM1 remained unchanged in THP-1 cells after the corresponding treatment. Our findings indicate that AIRE plays a role in the regulation of autophagy in THP-1 human monocytes.

Keywords

autoimmune regulator / autophagy / monocytes / light chain 3 (LC3)

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Liang SHI, Li-Hua HU, Yi-Rong LI. Autoimmune regulator regulates autophagy in THP-1 human monocytes. Front Med Chin, 2010, 4(3): 336‒341 https://doi.org/10.1007/s11684-010-0096-4

References

[1]
International Union of Immunological Societies Expert Committee on Primary Immunodeficiencies. NotarangeloL D, FischerA, GehaR S, CasanovaJ L, ChapelH, ConleyM E, Cunningham-RundlesC, EtzioniA, HammartrömL, NonoyamaS, OchsH D, PuckJ, RoifmanC, SegerR, WedgwoodJ. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol, 2009, 124(6): 1161–1178
[2]
AndersonM S, VenanziE S, KleinL, ChenZ, BerzinsS P, TurleyS J, von BoehmerH, BronsonR, DierichA, BenoistC, MathisD. Projection of an immunological self shadow within the thymus by the aire protein. Science, 2002, 298(5597): 1395–1401
CrossRef Google scholar
[3]
KogawaK, NagafuchiS, KatsutaH, KudohJ, TamiyaS, SakaiY, ShimizuN, HaradaM. Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol Lett, 2002, 80(3): 195–198
CrossRef Google scholar
[4]
RamseyC, HässlerS, MaritsP, KämpeO, SurhC D, PeltonenL, WinqvistO. Increased antigen presenting cell-mediated T cell activation in mice and patients without the autoimmune regulator. Eur J Immunol, 2006, 36(2): 305–317
CrossRef Google scholar
[5]
SillanpääN, MagureanuC G, MurumägiA, ReinikainenA, WestA, ManninenA, LahtiM, RankiA, SakselaK, KrohnK, LahesmaaR, PetersonP. Autoimmune regulator induced changes in the gene expression profile of human monocyte-dendritic cell-lineage. Mol Immunol, 2004, 41(12): 1185–1198
CrossRef Google scholar
[6]
MünzC. Enhancing immunity through autophagy. Annu Rev Immunol, 2009, 27: 423–449
CrossRef Google scholar
[7]
AkiyoshiH, HatakeyamaS, PitkänenJ, MouriY, DoucasV, KudohJ, TsurugayaK, UchidaD, MatsushimaA, OshikawaK, NakayamaK I, ShimizuN, PetersonP, MatsumotoM. Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. J Biol Chem, 2004, 279(32): 33984–33991
CrossRef Google scholar
[8]
KabeyaY, MizushimaN, UenoT, YamamotoA, KirisakoT, NodaT, KominamiE, OhsumiY, YoshimoriT. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J, 2000, 19(21): 5720–5728
CrossRef Google scholar
[9]
BlommaartE F, KrauseU, SchellensJ P, Vreeling-SindelárováH, MeijerA J. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem, 1997, 243(1-2): 240–246
CrossRef Google scholar
[10]
PankivS, ClausenT H, LamarkT, BrechA, BruunJ A, OutzenH, ØvervatnA, BjørkøyG, JohansenT. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem, 2007, 282(33): 24131–24145
CrossRef Google scholar
[11]
BjørkøyG, LamarkT, PankivS, ØvervatnA, BrechA, JohansenT. Monitoring autophagic degradation of p62/SQSTM1. Methods Enzymol, 2009, 452: 181–197
CrossRef Google scholar
[12]
GrayD, AbramsonJ, BenoistC, MathisD. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med, 2007, 204(11): 2521–2528
CrossRef Google scholar
[13]
González-PoloR A, BoyaP, PauleauA L, JalilA, LarochetteN, SouquèreS, EskelinenE L, PierronG, SaftigP, KroemerG. The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci, 2005, 118(Pt 14): 3091–3102
CrossRef Google scholar
[14]
UchidaD, HatakeyamaS, MatsushimaA, HanH, IshidoS, HottaH, KudohJ, ShimizuN, DoucasV, NakayamaK I, KurodaN, MatsumotoM. AIRE functions as an E3 ubiquitin ligase. J Exp Med, 2004, 199(2): 167–172
CrossRef Google scholar
[15]
HanadaT, NodaN N, SatomiY, IchimuraY, FujiokaY, TakaoT, InagakiF, OhsumiY. The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem, 2007, 282(52): 37298–37302
CrossRef Google scholar
[16]
ColosettiPPuissantA, RobertG, LucianoF, JacquelA, GounonP, CassutoJ P, AubergerP. Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line. Autophagy, 2009, 5(8): 1092–1098
CrossRef Google scholar
[17]
HongM, RyanK R, ArkwrightP D, GenneryA R, CostiganC, DominguezM, DenningD W, McConnellV, CantA J, AbinunM, SpickettG P, SwanD C, GillespieC S, YoungD A, LilicD. Pattern recognition receptor expression is not impaired in patients with chronic mucocutanous candidiasis with or without autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. Clin Exp Immunol, 2009, 156(1): 40–51
CrossRef Google scholar
[18]
PerniolaR, CongedoM, RizzoA, Sticchi DamianiA, FaneschiM L, PizzolanteM, LobreglioG. Innate and adaptive immunity in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Mycoses, 2008, 51(3): 228–235
CrossRef Google scholar

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