title: Evidence of immune system melatonin production by two pineal melatonin deficient mice, C57BL/6 and Swiss strains.
abstract: We evaluated two pineal melatonin deficient mice described in the literature, i.e., C57BL/6 and Swiss mice, as animal models for studying the immunomodulatory action of melatonin. Plasma melatonin levels in C57BL/6 and Swiss strains were detectable, but lower than levels in control C3H/HENHSD mice. Since these strains are suppose to be pineal melatonin deficient an extrapineal melatonin synthesis may contribute to plasma levels. Regarding cells and tissues from the immune system, all of them were found to synthesize melatonin although at low levels. N-acetyltransferase (AANAT) mRNA was also amplified in order to analyze the alternative splicing between exons 3-4 described for pineal C57BL/6 mice which generates an inclusion of a pseudoexon of 102 bp. For the pineal gland, both the wild type and the mutant isoforms were present in all mice strains although in different proportions. We observed a predominant wild type AANAT mature RNA in thymus, spleen and bone marrow cells. Peripheral blood mononuclear cells (PBMC) culture shown an evident AANAT amplification in all strains studied. Although the bands detected were less intense in melatonin deficient mice, the amplification almost reached the control cell intensity after stimulation with phytohemaglutinin (PHA). In summary, melatonin detection and AANAT mRNA expression in inbred and outbred mice clearly indicate that different cells and tissues from the immune system are able to synthesize melatonin. Thus, the pineal defect seems not to be generalized to all tissues, suggesting that other cells may compensate the low pineal melatonin production contributing to the measurable plasma melatonin level.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, The School of Medicine, University of Seville, Seville, Spain.
authors.forename: Araceli
authors.initials: A
authors.lastname: Gómez-Corvera
authors.forename: Isabel
authors.initials: I
authors.lastname: Cerrillo
authors.forename: Patrocinio
authors.initials: P
authors.lastname: Molinero
authors.forename: Maria Carmen
authors.initials: MC
authors.lastname: Naranjo
authors.forename: Patricia Judith
authors.initials: PJ
authors.lastname: Lardone
authors.forename: Marina
authors.initials: M
authors.lastname: Sanchez-Hidalgo
authors.forename: Maria Pilar
authors.initials: MP
authors.lastname: Carrascosa-Salmoral
authors.forename: Pablo
authors.initials: P
authors.lastname: Medrano-Campillo
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Guerrero
authors.forename: Amalia
authors.initials: A
authors.lastname: Rubio
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001853:Bone Marrow / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D007107:Immune System / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008550:Melatonin / Q000096:biosynthesis* / Q000097:blood / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010835:Phytohemagglutinins / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000201:enzymology / Q000378:metabolism; D013950:Thymus Gland / Q000201:enzymology / Q000378:metabolism
chemical_list: D010835:Phytohemagglutinins; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin