title: Testosterone response of hepatic gene expression in female mice having acquired testosterone-unresponsive immunity to Plasmodium chabaudi malaria.
abstract: Blood-stage malaria of Plasmodium chabaudi is characterized by its responsiveness to testosterone (T): T suppresses development of protective immunity, whereas once acquired immunity is T-unresponsive. Here, we have analyzed the liver, a T target and lymphoid organ with anti-malaria activity, for its T-responsiveness of gene expression in immune mice. Using Affymetrix microarray technology, in combination with quantitative RT-PCR, we have identified (i) T-unresponsive expression of newly acquired mRNAs encoding diverse sequences of IgG- and IgM-antibodies, (ii) 24 genes whose expression has become T-unresponsive including those encoding the T(H)2 response promoting EHMT2 and the erythrocyte membrane protein band 7.2 STOM, (iii) T-unresponsive expression of mRNAs for the cytokines IL-1β, IL-6, TNFα, and IFNγ, as well as iNOS, which are even not inducible by infection, and (iv) 35 genes retaining their T-responsiveness, which include those encoding the infection-inducible acute phase proteins SAA1, SAA2, and ORM2 as well as those of liver metabolism which encode the T-downregulated female-prevalent enzymes CYP2B9, CYP2B13, CYP3A41, CYP7A1, and SULT2A2 and the T-upregulated male-prevalent enzymes CYP2D9, CYP7B1, UGT2B1, HSD3B2, HSD3B5, respectively. The mRNA of the latter T-metabolizing enzyme is even 5-fold increased by T, suggesting a decrease in the effective T concentrations in the liver of immune mice. Collectively, our data suggest that the liver, which has acquired a selective T-unresponsiveness of gene expression, contributes to the acquired T-unresponsive, antibody-mediated protective immunity to blood-stage malaria of P. chabaudi.
authors.affiliation: Division of Molecular Parasitology and Centre for Biological and Medical Research, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Duesseldorf, Germany. denisdelic@aol.com
authors.forename: D
authors.initials: D
authors.lastname: Delić
authors.forename: H
authors.initials: H
authors.lastname: Ellinger-Ziegelbauer
authors.forename: H W
authors.initials: HW
authors.lastname: Vohr
authors.forename: M
authors.initials: M
authors.lastname: Dkhil
authors.forename: S
authors.initials: S
authors.lastname: Al-Quraishy
authors.forename: F
authors.initials: F
authors.lastname: Wunderlich
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000818:Animals; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008288:Malaria / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016788:Plasmodium chabaudi / Q000276:immunology*; D016133:Polymerase Chain Reaction; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D015850:Interleukin-6; D013739:Testosterone