Bromelain treatment reduces CD25 expression on activated CD4+ T cells in vitro

Abstract

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.

Isolation and purification of bromelain from waste peel of pineapple for therapeutic application

“…Due to its proteolytic activity, bromelain has been extensively used in therapeutic applications in several animal models (Ahle 1987;Bahde 2007;Bhui et al 2009). A wide range of therapeutic benefits have been attributed to bromelain due to its action as therapeutic target in inflammation, autoimmunity and allergy, as well as the reversible inhibition of platelet aggregation, bronchitis relief, improved recovery after surgical traumas, and enhanced absorption of drugs, particularly of antibiotics (Kelly 1996;Murakawa 2002;Roep 2002;Secor 2009). Enzymatic debridement of necrotic tissues from ulcers, burn wounds and frostbite eschar as well as anti-proliferative and anti-metastatic effects in tumor models have been also studied (Ahle 1987;Napper et al 1994;Bhui et al 2009).…”

Icaritin inhibits T cell activation and prolongs skin allograft survival in mice

“…Following the stimulation, the activation maker such as CD25 can be upregulated. As the high affinity alpha chain of IL-2 receptor, the binding of CD25 to the IL-2 can trigger a cascade response, resulting in T cell proliferation and additional IL-2 production [16]. IL-2 is also defined as a Th1 cytokine.…”

“…secreted by activated T helper cells or a higher Th1/Th2 ratio in various of immune overwhelming diseases, such as autoimmune, allergy and transplantation rejection [17][18][19]. Therapeutic interventions to such diseases are often designed to reduce the threshold of T cell activation [16]. Therefore, immnosuppressive drugs, like cyclosporine A (CsA) and dexamethasone (Dex), are often used in these immune overwhelming diseases [20,21] In the present study, we found that icaritin at a quite low concentration could act as an immunosuppressant to reduce T cell proliferation, IL-2/CD25 expression, and Th1 cytokines production in vitro.…”

Asthma in the 21st Century — Unexpected Applications of Ancient Treatments

“…In a study using peripheral blood mononuclear cells (PBMC), Bromelain decreases the expression of migration/activation related cell surface markers on leukocyte by proteolysis, including CD14, CD16, CD21, CD25, CD44, CD45RA, CD62L [263]. In addition, it can dosedependently reduce CD25 expression in anti-CD3 antibody-stimulated CD4 + T cells, which is upregulated when T cells are activated in inflammation, autoimmunity and allergy [264].…”