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2099-12-31
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IL-4 AND IL-13 REGULATE THE INDUCTION OF INDOLEAMINE 2,3-DIOXYGENASE ACTIVITY AND THE CONTROL OF TOXOPLASMA GONDII REPLICATION IN HUMAN FIBROBLASTS ACTIVATED WITH IFN-GAMMA.
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Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Department of Biochemistry and Immunology. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil
Abstract
The ability of up-regulatory [recombinant (r) IFN- , rIFN- and rTNF- ¼] and down-regulatory (rIL-4, rIL-10 and rIL-13) cytokines to control the expression of indoleamine 2,3-dioxygenase (INDO) and anti-Toxoplasma activity in the human fibrosarcoma cell line 2C4 was evaluated. Activation of fibroblasts with rIFN- , rIFN- and rTNF- ¼resulted in augmentation of INDO expression and activity leading to 40.0, 25.0 and 27.0 % inhibition of tachyzoite growth, respectively. An additive effect was observed when host cells were incubated with rIFN- plus rTNF- ¼. With regard to the down-regulatory cytokines we observed that IL-4 as well as IL-13, but not IL-10, induced significant inhibition of IFN- -induced control of parasite replication, INDO mRNA expression and tryptophan catabolism. Similarly, IL-4 but not IL-10 inhibited the cell surface expression of HLA-DR and CD2 induced by IFN- . Consistent with these findings we were able to detect by reverse transcription-PCR the expression of mRNA for different chains of IL-4 and IL-13 receptors (IL-4R ¼, IL-13R ¼1 and IL-13R ¼2) but not for IL-10 receptor in the 2C4 and other human lung fibroblast cell lines (LL24 and MRC5). Together our results indicate that IL-4 and IL-13, but not IL-10, are implicated in the negative regulation of IFN- -induced anti-Toxoplasma activity in human cells from fibroblast lineage.
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