Melatonin attenuates Leishmania (L.) amazonensis infection by modulating arginine metabolism

被引:46
作者
Laranjeira-Silva, Maria Fernanda [1 ]
Zampieri, Ricardo A. [1 ]
Muxel, Sandra M. [1 ]
Floeter-Winter, Lucile Maria [1 ]
Markus, Regina P. [1 ]
机构
[1] Univ Sao Paulo, Inst Biosci, BR-05508900 Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
arginase; cationic amino acid transporter; macrophage; nitric oxide synthase; polyamines; NITRIC-OXIDE SYNTHASE; IMMUNE-PINEAL AXIS; INHIBITS EXPRESSION; MURINE MACROPHAGES; INDUCIBLE ISOFORM; HUMAN COLOSTRUM; TNF-ALPHA; ANTIOXIDANT; CELLS; GLAND;
D O I
10.1111/jpi.12279
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Acute inflammatory responses induced by bacteria or fungi block nocturnal melatonin synthesis by rodent pineal glands. Here, we show Leishmania infection does not impair daily melatonin rhythm in hamsters. Remarkably, the attenuated parasite burden and lesion progression in hamsters infected at nighttime was impaired by blockage of melatonin receptors with luzindole, whereas melatonin treatment during the light phase attenuated Leishmania infection. In vitro studies corroborated in vivo observations. Melatonin treatment reduced macrophage expression of Cat-2b, Cat1, and ArgI, genes involved in arginine uptake and polyamine synthesis. Indeed, melatonin reduced macrophage arginine uptake by 40%. Putrescine supplementation reverted the attenuation of infectivity by melatonin indicating that its effect was due to the arrest of parasite replication. This study shows that the Leishmania/host interaction varies in a circadian manner according to nocturnal melatonin pineal synthesis. Our results provide new data regarding Leishmania infectiveness and show new approaches for applying agonists of melatonin receptors in Leishmaniasis therapy.
引用
收藏
页码:478 / 487
页数:10
相关论文
共 55 条
[1]   Melatonin inhibits the expression of the inducible isoform of nitric oxide synthase and nuclear factor kappa B activation in rat skeletal muscle [J].
Alonso, Maria ;
Collado, Pilar S. ;
Gonzalez-Gallego, Javier .
JOURNAL OF PINEAL RESEARCH, 2006, 41 (01) :8-14
[2]   Melatonin modulates microsomal PGE synthase 1 and NF-E2-related factor-2-regulated antioxidant enzyme expression in LPS-induced murine peritoneal macrophages [J].
Aparicio-Soto, M. ;
Alarcon-de-la-Lastra, C. ;
Cardeno, A. ;
Sanchez-Fidalgo, S. ;
Sanchez-Hidalgo, M. .
BRITISH JOURNAL OF PHARMACOLOGY, 2014, 171 (01) :134-144
[3]   Leishmaniasis reservoirs and their significance in control [J].
Ashford, RW .
CLINICS IN DERMATOLOGY, 1996, 14 (05) :523-532
[4]   Nitric oxide biosynthesis, nitric oxide synthase inhibitors and arginase competition for L-arginine utilization [J].
Boucher, JL ;
Moali, C ;
Tenu, JP .
CELLULAR AND MOLECULAR LIFE SCIENCES, 1999, 55 (8-9) :1015-1028
[5]   The role of melatonin in the cells of the innate immunity: a review [J].
Calvo, Juan R. ;
Gonzalez-Yanes, C. ;
Maldonado, M. D. .
JOURNAL OF PINEAL RESEARCH, 2013, 55 (02) :103-120
[6]   Evidence of melatonin synthesis by human lymphocytes and its physiological significance:: possible role as intracrine, autocrine, and/or paracrine substance [J].
Carrillo-Vico, A ;
Calvo, JR ;
Abreu, P ;
Lardone, PJ ;
García-Mauriño, S ;
Reiter, RJ ;
Guerrero, JM .
FASEB JOURNAL, 2004, 18 (01) :537-+
[7]   Melatonin: Buffering the Immune System [J].
Carrillo-Vico, Antonio ;
Lardone, Patricia J. ;
Alvarez-Sanchez, Nuria ;
Rodriguez-Rodriguez, Ana ;
Guerrero, Juan M. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (04) :8638-8683
[8]  
Carvalho-Sousa C.E., 2011, FR ENDOCRINOL, V2, P1, DOI DOI 10.3389/FENDO.2011.00010
[9]   ARGINASE INDUCTION BY SUPPRESSORS OF NITRIC-OXIDE SYNTHESIS (IL-4, IL-10 AND PGE(2)) IN MURINE BONE-MARROW-DERIVED MACROPHAGES [J].
CORRALIZA, IM ;
SOLER, G ;
EICHMANN, K ;
MODOLELL, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 206 (02) :667-673
[10]   Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide-induced multiple organ dysfunction syndrome in rats [J].
Crespo, E ;
Macías, M ;
Pozo, D ;
Escames, G ;
Martin, M ;
Vives, F ;
Guerrero, JM ;
Acuña-Castroviejo, D .
FASEB JOURNAL, 1999, 13 (12) :1537-1546