On cell signalling mechanism of Mycobacterium leprae soluble antigen (MLSA) in Jurkat T cells.
We investigated the role of Mycobaterium leprae soluble antigen (MLSA) in the modulation of calcium signalling, phosphorylation of mitogen-activated protein (MAP) kinases and IL-2 mRNA expression in human Jurkat T cells. We observed that MLSA induced an increase in free intracellular calcium concentrations, [Ca2+]i, via opening CRAC (Ca2+-release activated- Ca2+) channels. Furthermore, MLSA failed to potentiate both thapsigargin- and anti-CD3 antibodies-induced capacitative calcium influx in Jurkat T cells. We observed that MLSA failed to affect the degree of phosphorylation of two MAP kinases, i.e., ERK1/ERK2, stimulated by anti-CD3 antibodies alone or phorbol 12-myristate 13-acetate (PMA) alone. In order to mimic co-stimulation of T cells, we stimulated them by both PMA and anti-CD3 antibodies. MLSA significantly curtailed the phosphorylation of ERK1/ERK2, stimulated by both PMA and anti-CD3 antibodies in Jurkat T cells. Also MLSA was found to reduce the transcription of IL-2 gene in PMA plus anti-CD3 antibodies-activated Jurkat T cells. Our finding demonstrates that Ca2+ influx via CRAC channels, inhibition of ERK1/ERK2 phosphorylation and IL-2 gene transcription may be implicated in immunosuppressive effects of MLSA antigen.
Joshi
Beenu
B
Central JALMA Institute for Leprosy and other Mycobacterial Diseases (ICMR), Taj Ganj, Agra, U.P, 282001, India.
Khedouci
Sihem
S
Dagur
Pradeep Kumar
PK
Hichami
Aziz
A
Sengupta
Utpal
U
Khan
Naim Akhtar
NA
D000942:Antigens, Bacterial / Q000302:isolation & purification / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects*; D009166:Mycobacterium leprae / Q000276:immunology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000942:Antigens, Bacterial; D015220:Calcium Channels; D007376:Interleukin-2; D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium