Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro.
Bromelain (Br), an extract from pineapple stem with cysteine protease activity, exerts anti-inflammatory effects in a number of inflammatory models. We have previously shown that Br treatment decreased activated CD4(+) T cells and has a therapeutic role in an ovalbumin-induced murine model of allergic airway disease. The current study was designed to determine the effect of Br on CD4(+) T cell activation, specifically the expression of CD25 in vitro. CD25 is up regulated upon T cell activation, found as a soluble fraction (sCD25) and is a therapeutic target in inflammation, autoimmunity and allergy. Br treatment of anti-CD3 stimulated CD4(+) T cells reduced CD25 expression in a dose and time dependent manner. This reduction of CD25 was dependent on the proteolytic action of Br as the addition of E64 (a cysteine protease inhibitor) abrogated this response. The concentration of sCD25 was increased in supernatants of Br treated activated CD4(+) T cells as compared to control cells, suggesting that Br proteolytically cleaved cell-surface CD25. This novel mechanism of action identifies how Br may exert its therapeutic benefits in inflammatory conditions.
Secor
Eric R
ER
Department of Immunology, University of Connecticut Health Center 263 Farmington Ave, MC1319Farmington, CT 06030, USA. esecor@uchc.edu
Singh
Anurag
A
Guernsey
Linda A
LA
McNamara
Jeff T
JT
Zhan
Lijun
L
Maulik
Nilanjana
N
Thrall
Roger S
RS
D031230:Ananas / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001963:Bromelains / Q000737:chemistry / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002457:Cell Extracts / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D053645:Interleukin-2 Receptor alpha Subunit / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002457:Cell Extracts; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D001963:Bromelains