Tumor-induced thymic involution via inhibition of IL-7R alpha and its JAK-STAT signaling pathway: protection by black tea.

Abstract

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.

• Authors: Debaprasad Mandal, Lakshmishri Lahiry, Arindam Bhattacharyya, Sankar Bhattacharyya, Gaurisankar Sa, Tanya Das
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 6 Issue 3 Pg. 433-44 (Mar 2006) ISSN: 1567-5769 [Print] Netherlands
• PMID: 16428079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Plant Extracts
• Receptors, Interleukin-7
• STAT5 Transcription Factor
• Tea
• interleukin-7 receptor, alpha chain
• Janus Kinase 3

Topics

• Animals
• Apoptosis (physiology)
• CD4-Positive T-Lymphocytes (drug effects, immunology, pathology)
• CD8-Positive T-Lymphocytes (drug effects, immunology, pathology)
• Camellia sinensis
• Carcinoma, Ehrlich Tumor (enzymology, immunology, pathology, prevention & control)
• Cell Line, Tumor
• Cells, Cultured
• Janus Kinase 3 (antagonists & inhibitors, physiology)
• Leukocyte Count
• Leukocytes, Mononuclear (drug effects, immunology, pathology)
• Lymphocyte Count
• MAP Kinase Signaling System (immunology)
• Mice
• Phosphorylation
• Plant Extracts (therapeutic use)
• Receptors, Interleukin-7 (antagonists & inhibitors, physiology)
• STAT5 Transcription Factor (antagonists & inhibitors, physiology)
• Tea (chemistry)
• Thymus Gland (drug effects, enzymology, immunology, pathology)