The role of nitric oxide in the epigenetic regulation of THP-1 induced by lipopolysaccharide
Carregando...
Citações na Scopus
13
Tipo de produção
article
Data de publicação
2016
Título da Revista
ISSN da Revista
Título do Volume
Editora
PERGAMON-ELSEVIER SCIENCE LTD
Citação
LIFE SCIENCES, v.147, p.110-116, 2016
Resumo
Aims: Changes in the gene expression are one of the molecular events involved in the Systemic of Inflammatory Response Syndrome during sepsis. The preconditioning with low doses of lipopolysaccharide (LPS) reduces the expression of pro-inflammatory genes leading to less tissue damage and better outcome. This hyporesponsive state called tolerance is associated to alterations in chromatin structure and nitric oxide (NO) production. In the current study, we demonstrated that tolerance induced by LPS was found to be NO-dependent and related to epigenetic changes. Main methods: THP-1 cells were cultivated in RPMI medium(Control), submitted to tolerance (500 ng/mL of LPS 24 h before challenge with 1000 ng/mL of LPS during 24 h Tolerant group) and challenge (1000 ng/mL of LPS during 24 h Directly challenged group). The analyses performed were: cytokines production, histone acetyl transferases/histone deacetylases (HAT/HDAC) activity, nitrosylation of HDAC-2 and -3, expression of acetylated histones H3 and H4. HDAC and Nitric Oxide Synthases (NOS) activities were inhibited with 30 mM trichostatin (TSA) and 100 mu M LNAME, respectively. Key findings: Administration of low doses of LPS repressed the production of IL-6 and IL-10, however this effect was abolished with the inhibition of NOS activity and by TSA in the case of IL-10. Tolerance modulates the activity of HAT and, consequently, the acetylation of histones H3 and H4. Inhibition of NO decreases acetylation of Histones. The HDACs 2 and 3 were nitrosylated after the tolerance induction. Significance: The tolerance to LPS regulates the cytokine production by modulating chromatin structure and this event is NO dependent.
Palavras-chave
Endotoxin, Tolerance, Gene transcription, Endotoxemia
Referências
- Kimura H, 2001, J CELL BIOL, V153, P1341, DOI 10.1083/jcb.153.7.1341
- West MA, 2002, CRIT CARE MED, V30, pS64, DOI 10.1097/00003246-200201001-00009
- PADGETT CM, 1995, AM J PHYSIOL-CELL PH, V269, pC739
- Lorigados Clara Batista, 2010, Endocrine Metabolic & Immune Disorders-Drug Targets, V10, P274
- Tomita T, 2000, RHEUMATOLOGY, V39, P749, DOI 10.1093/rheumatology/39.7.749
- Hoffmann J, 2003, FEBS LETT, V551, P153, DOI 10.1016/S0014-5793(03)00917-7
- Foster SL, 2007, NATURE, V447, P972, DOI 10.1038/nature05836
- Kornberg MD, 2010, NAT CELL BIOL, V12, P1094, DOI 10.1038/ncb2114
- Hess DT, 2005, NAT REV MOL CELL BIO, V6, P150, DOI 10.1038/nrm1569
- Riccio A, 2006, MOL CELL, V21, P283, DOI 10.1016/j.molcel.2005.12.006
- Fields PE, 2002, J IMMUNOL, V169, P647
- Vanden Berghe W, 1999, J BIOL CHEM, V274, P32091, DOI 10.1074/jbc.274.45.32091
- Huang Q, 2001, SCIENCE, V294, P870, DOI 10.1126/science.294.5543.870
- Guha M, 2001, CELL SIGNAL, V13, P85, DOI 10.1016/S0898-6568(00)00149-2
- Nott A, 2013, P NATL ACAD SCI USA, V110, P3113, DOI 10.1073/pnas.1218126110
- Hausladen A, 1996, CELL, V86, P719, DOI 10.1016/S0092-8674(00)80147-6
- Grozinger CM, 2002, CHEM BIOL, V9, P3, DOI 10.1016/S1074-5521(02)00092-3
- Glozak MA, 2005, GENE, V363, P15, DOI 10.1016/j.gene.2005.09.010
- Hara MR, 2005, NAT CELL BIOL, V7, P665, DOI 10.1038/ncb1268
- Northrop JK, 2006, J IMMUNOL, V177, P1062
- Yu ZT, 2002, J AM SOC NEPHROL, V13, P2009, DOI 10.1097/01.ASN.0000024253.59665.F1
- Beutler B, 2003, NAT REV IMMUNOL, V3, P169, DOI 10.1038/nri1004
- Struhl K, 1998, GENE DEV, V12, P599, DOI 10.1101/gad.12.5.599
- Chan C, 2005, J IMMUNOL, V175, P461
- Pakala SB, 2010, J BIOL CHEM, V285, P23590, DOI 10.1074/jbc.M110.139469
- Anand P, 2012, J MOL MED, V90, P233, DOI 10.1007/s00109-012-0878-z
- Melo ES, 2010, IMMUNOBIOLOGY, V215, P435, DOI 10.1016/j.imbio.2009.09.002
- Macdonald J, 2003, BRIT J ANAESTH, V90, P221, DOI 10.1093/bja/aeg034
- Melo ES, 2010, MOL IMMUNOL, V47, P2587, DOI 10.1016/j.molimm.2010.06.011
- Fang M, 2000, NEURON, V28, P183, DOI 10.1016/S0896-6273(00)00095-7
- Hall MJ, 2011, NCHS DATA BRIEF, V62, P1
- Iwakiri Y., 2006, P NATL ACAD SCI USA, V103, P19777
- Nott A, 2008, NATURE, V455, P411, DOI 10.1038/nature07238
- Sun J., 2001, P NATL ACAD SCI USA, V98, P11158