Abrogation of delayed type hypersensitivity response to Candida albicans produced by a molecular mimic of phosphorylated prolactin

The effects of two major forms of prolactin (PRL) were examined on delayed type hypersensitivity (DTH) responses to Candida albicans. Unmodified PRL (U-PRL) had no effect on the DTH response, whereas a molecular mimic of phosphorylated PRL (S179D PRL) significantly inhibited immune responses to this...

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Bibliographic Details
Published in:	Journal of neuroimmunology Vol. 170; no. 1; pp. 31 - 40
Main Authors:	Guzmán, E.A., Chen, Y.-H., Langowski, J.L., De Guzman, A., Lo, H.-L., Walter, B., Muller, H.K., Walker, A.M., Owen, L.B.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 30-12-2005
Subjects:	Animals Anti-flammatory Antibodies, Fungal - immunology Antibody Formation - drug effects Apoptosis - drug effects Candida albicans Candida albicans - immunology Cytokines Cytokines - antagonists & inhibitors Delayed type hypersensitivity Fas ligand Fas Ligand Protein Hypersensitivity, Delayed - immunology Hypersensitivity, Delayed - physiopathology Immunoglobulin G - metabolism Inflammation Mediators - antagonists & inhibitors Lymph Nodes - metabolism Male Membrane Glycoproteins - metabolism Mice Mice, Inbred Strains Molecular Mimicry Phosphorylated prolactin Phosphorylation Prolactin - metabolism Prolactin - pharmacology Spleen - pathology Spleen - physiopathology Tumor Necrosis Factors - metabolism Fas ligand Anti-flammatory Delayed type hypersensitivity Cytokines Phosphorylated prolactin
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Summary:	The effects of two major forms of prolactin (PRL) were examined on delayed type hypersensitivity (DTH) responses to Candida albicans. Unmodified PRL (U-PRL) had no effect on the DTH response, whereas a molecular mimic of phosphorylated PRL (S179D PRL) significantly inhibited immune responses to this robust antigen. This effect of S179D PRL was not accompanied by gross alterations in splenic T cell numbers, CD4 / CD8 ratios, or T and B cell activation markers, but did produce a decrease in splenocyte apoptosis. Using gld animals, Fas ligand (FasL) was implicated in the suppressive effects of S179D PRL. Circulating IgG 1 and IgG 2 antibody levels were increased in response to treatment with both forms of PRL, but the effects of S179D PRL were most pronounced. Cytokine changes in the popliteal lymph nodes specific to S179D PRL treatment showed an inhibition of pro-inflammatory cytokines. In conclusion, mice treated with a molecular mimic of phosphorylated prolactin showed a profound inhibition of DTH responses to Candida correlating with an absence of GM-CSF, IL-4, and IL-13 production and a marked reduction in IL-12p70 synthesis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0165-5728 1872-8421
DOI:	10.1016/j.jneuroim.2005.08.009