ABSTRACT
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 IgG1 and IgG2 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.
Subject(s)
Candida albicans/immunology , Hypersensitivity, Delayed/immunology , Molecular Mimicry , Phosphorylation , Prolactin/metabolism , Prolactin/pharmacology , Animals , Antibodies, Fungal/immunology , Antibody Formation/drug effects , Apoptosis/drug effects , Cytokines/antagonists & inhibitors , Fas Ligand Protein , Hypersensitivity, Delayed/physiopathology , Immunoglobulin G/metabolism , Inflammation Mediators/antagonists & inhibitors , Lymph Nodes/metabolism , Male , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred Strains , Spleen/pathology , Spleen/physiopathology , Tumor Necrosis Factors/metabolismABSTRACT
Apoptosis plays a critical role in the development and progression of ultraviolet-induced skin cancers. In particular, Fas and Fas ligand (FasL) interactions are known to control the development of "sunburn cells" or apoptotic keratinocytes in the UV-exposed epidermis. In the absence of functional Fas/FasL signaling, UV-induced apoptosis is diminished and mutations rapidly accumulate. UV-induced suppression of host immunity, a process regulating skin cancer outgrowth, is also controlled through Fas/FasL interactions. Other death receptors, such as the receptor for tumor necrosis factor, may also contribute to UV-induced carcinogenesis and progression. Understanding the involvement of cell death in cancers caused by exposure to sunlight may provide novel approaches for prevention and therapy of these ever-increasing malignancies.
