Differential regulation of the protein tyrosine kinase activity following interleukin-2 (IL-2), interferron gamma (IFN-gamma) and SRBC administration in brain tumor-induced conditions: SRBC acting as a dual potentiator in regulating the cytokine profile.
Protein tyrosine kinases (PTKs) act as an important class of signal transducer in cytokine mediated signaling. Defects in phosphorylation of tyrosine residues of intracellular substrates of the immunocytes are a noted phenomenon in glioma induced immune suppression. Administration of BRMs like Interleukin2 (IL-2), Interferon gamma (IFN-gamma) and SRBC in glioma induced experimental models, improved their survival status by immune potentiation. It was shown that SRBC exerts the maximum anti-tumor immune boosting by augmenting the functional status of the two immunocytes-microglia and lymphocytes when compared with IL-2 and IFN-gamma. The present study focuses on the differential modulation of the protein tyrosine kinase activity in lymphocytes and microglia following the administration of the 3 BRMs. Our findings indicate that PTKs actively transduce signals on administration of exogenous IL-2. But exogenous IFN-gamma administration fails to elicit the enzyme activity. With SRBC administration, a differential PTK activity modulation was observed in the two immunocytes. SRBC not only shifted the cytokine profile to Th1 subset of lymphocytes but also simultaneously upregulated the expression of the activation marker IL-2Ralpha/CD25 thereby resulting in auto-activation of the hosts immunocytes.
Bhattacharjee
M
M
Cellular and Molecular Immunology Lab, Department of Physiology, Dr. B.C. Roy Postgraduate Institute of Basic Medical Sciences, Institute of Postgraduate Medical Education and Research, Kolkata, India.
Sarkar
S
S
Dutta
S
S
Begum
Z
Z
Roy
U R
UR
Chaudhuri
Samares
S
Chaudhuri
Swapna
S
D000818:Animals; D000831:Animals, Newborn; D001932:Brain Neoplasms / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D002478:Cells, Cultured; D005038:Ethylnitrosourea / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic; D007111:Immunity, Cellular; D007155:Immunologic Factors / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D053645:Interleukin-2 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins / Q000008:administration & dosage*; D008214:Lymphocytes / Q000201:enzymology; D017628:Microglia / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D018123:Receptors, Interleukin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism
C105104:Cavin3 protein, rat; D007155:Immunologic Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D047908:Intracellular Signaling Peptides and Proteins; D018123:Receptors, Interleukin; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D005038:Ethylnitrosourea