Tumor-induced thymic involution via inhibition of IL-7R alpha and its JAK-STAT signaling pathway: protection by black tea.
Down-regulation of cell-mediated immune functions occurring at late stages of cancer may be related to the thymic involution since thymus is the major site of T cell maturation, proliferation, and differentiation. We found that in Ehrlich's ascites carcinoma (EAC)-bearing mice there was profound depletion of CD4+ and CD8+ cells in peripheral blood with severely damaged thymus on 21st day of tumor inoculation. However, treatment with black tea at an antitumor dose of 2.5% significantly reduced such depletion and protected the thymus considerably from tumor onslaught. A search for the underlying mechanism revealed EAC-induced IL-7Ralpha down-regulation, inhibition of JAK3 and STAT5 phosphorylation, and decrease in Bcl-2/Bax ratio in thymocytes that finally led to thymocyte apoptosis in one hand and T cell maturation block on the other. Interestingly, black tea treatment prevented IL-7Ralpha down-regulation and protected the signaling cascade through JAK-STAT thereby inhibiting tumor-induced thymic apoptosis and ensuring proper functioning of this organ in tumor-bearing host.
Mandal
Debaprasad
D
Bose Institute, P-1/12 CIT Scheme VII M, Kolkata-700 054, India.
Lahiry
Lakshmishri
L
Bhattacharyya
Arindam
A
Bhattacharyya
Sankar
S
Sa
Gaurisankar
G
Das
Tanya
T
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D028241:Camellia sinensis; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors* / Q000502:physiology; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D020935:MAP Kinase Signaling System / Q000276:immunology*; D051379:Mice; D010766:Phosphorylation; D010936:Plant Extracts / Q000627:therapeutic use; D020395:Receptors, Interleukin-7 / Q000037:antagonists & inhibitors* / Q000502:physiology; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D013662:Tea / Q000737:chemistry; D013950:Thymus Gland / Q000187:drug effects / Q000201:enzymology / Q000276:immunology / Q000473:pathology*
D010936:Plant Extracts; D020395:Receptors, Interleukin-7; D050799:STAT5 Transcription Factor; D013662:Tea; C415350:interleukin-7 receptor, alpha chain; D053616:Janus Kinase 3