Tumor associated release of interleukin-10 alters the prolactin receptor and down-regulates prolactin responsiveness of immature cortical thymocytes.
The soluble factors produced either by Ehrlich's ascites carcinoma (EAC) or thymic adherent cells (TAC) of tumor-bearing mice comprising of CD11b(+) and CD11c(+) antigen-presenting cells caused a sharp decrease in prolactin (PRL)-induced ConA-mediated effect on survival of PNA(+) thymocytes. Similar suppression of PRL-induced effect was observed when the cells were cocultured with TAC of EAC-bearing mice. Anti-IL-10 antibody could reverse the PRL inability to induce ConA-mediated effect on PNA(+) thymocyte survival, indicating the presence of IL-10 in EAC culture supernatant (EAC sup) and thymic microenvironment. IL-10 could block PRL-induced proliferation of PNA(+) thymocytes without affecting spontaneous apoptosis. IL-10 altered the expression of the long-form (LF) of PRL-R and reduced the PRL binding of the cells, suggesting down-regulation of the PRL effect on PNA(+) thymocyte by the cytokine. Induction of tumor, which was found to increase the IL-10 secretion by TAC, also modified the PRL-R (LF) to PRL-R (SF). Since PRL plays a role in survival, proliferation and differentiation of lymphoid progenitor cells, the tuning of PRL action by IL-10 may be a possible mechanism of depletion of immature cortical thymocytes and thymic atrophy in tumor-bearing mice.
Roy
Tanima
T
Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata-700 026, West Bengal, India.
Paul
Sonali
S
Baral
Rathindra Nath
RN
Chattopadhyay
Utpala
U
Biswas
Ratna
R
D000818:Animals; D017209:Apoptosis; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002453:Cell Cycle; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D044708:DNA, Concatenated / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D009368:Neoplasm Transplantation / Q000379:methods; D019887:Peanut Agglutinin; D011388:Prolactin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D017077:Culture Media, Conditioned; D044708:DNA, Concatenated; D019887:Peanut Agglutinin; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D016753:Interleukin-10; D011388:Prolactin