17β-ESTRADIOL INCREASES LEISHMANIA MEXICANA KILLING IN MACROPHAGES FROM DBA/2 MICE BY ENHANCING PRODUCTION OF NITRIC OXIDE BUT NOT PRO-INFLAMMATORY CYTOKINES

We have previously shown that female DBA/2 mice are significantly more resistant to Leishmania mexicana compared with males. Here, we have analyzed the effect of 17β-estradiol (E2) on function and cytokine production in male and female DBA/2 macrophages in vitro. We show that E2 increases NO production and parasite killing in L. mexicana-infected male and female DBA/2 macrophages without increasing production of pro-inflammatory cytokines. These data indicate that E2 may enhance leishmanicidal activity in macrophages by directly regulating production of NO.

[1]  S. Oghumu,et al.  Sex‐associated Susceptibility in Humans with Chiclero's Ulcer: Resistance in Females is Associated with Increased Serum‐levels of GM‐CSF , 2007, Scandinavian journal of immunology.

[2]  C. Lezama-Dávila,et al.  Systemic cytokine response in humans with chiclero’s ulcers , 2006, Parasitology Research.

[3]  Yali Hu,et al.  Effects of 17beta-estradiol on the maturation, nuclear factor kappa B p65 and functions of murine spleen CD11c-positive dendritic cells. , 2006, Molecular immunology.

[4]  L. Ignarro,et al.  Rapid nitric oxide-mediated S-nitrosylation of estrogen receptor: regulation of estrogen-dependent gene transcription. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Straub,et al.  Synovial fluid estrogens in rheumatoid arthritis. , 2004, Autoimmunity reviews.

[6]  H. Jeong,et al.  17 beta-estradiol increases inducible nitric oxide synthase expression in macrophages. , 2003, Biochemical and biophysical research communications.

[7]  A. Satoskar,et al.  Susceptibility to Leishmania mexicana infection is due to the inability to produce IL‐12 rather than lack of IL‐12 responsiveness , 2001, Immunology and cell biology.

[8]  J. S. Hunt,et al.  Sex steroid hormones and macrophage function. , 1996, Life sciences.

[9]  R J Walter,et al.  Steroid sex hormones regulate the release of tumor necrosis factor by macrophages. , 1995, Cellular immunology.

[10]  J. Alexander,et al.  Sex-determined susceptibility and differential IFN-gamma and TNF-alpha mRNA expression in DBA/2 mice infected with Leishmania mexicana. , 1995, Immunology.

[11]  M. Sorci-Thomas,et al.  Estrogen modulates the expression of tumor necrosis factor alpha mRNA in phorbol ester-stimulated human monocytic THP-1 cells. , 1994, Lymphokine and cytokine research.

[12]  W. Stimson,et al.  Oestrogen Receptors in Macrophages , 1990, Scandinavian journal of immunology.

[13]  W. H. Stimson.  Oestrogen and Human T Lymphocytes: Presence of Specific Receptors in the T‐Suppressor/Cytotoxic Subset , 1988, Scandinavian journal of immunology.

[14]  P. Musiani,et al.  Estrogen binding sites in peripheral blood mononuclear cells and thymocytes from 2 myasthenia gravis patients. , 1986, Journal of clinical & laboratory immunology.

[15]  G. Lenoir,et al.  Distribution of androgen and estrogen receptors among lymphoid and haemopoietic cell lines. , 1985, Leukemia research.