Modulation of cytokine production by plant sterols in stimulated human Jurkat T cells

Abstract

The plant sterols campesterol, beta-sitosterol and beta-sitostanol were investigated for potential immunomodulatory effects in Jurkat T cells. Treatments involved supplementing cells with or without concanavalin A (ConA) or phorbol-12-myristate-13-acetate plus ionomycin (PMA+IoM) in the presence or absence of increasing concentrations (10-100 microM) of each plant sterol for 24 h. None of the plant sterols significantly affected mitogen-stimulated IL-4, IL-10 or IFN-gamma production. However, campesterol, beta-sitosterol and beta-sitostanol significantly suppressed mitogen-induced IL-2 production in a dose-dependent manner. Both bisindolylmaleimide-I (BIM-I), a specific protein kinase C (PKC) inhibitor, and the immunosuppressant drug known as Tacrolimus (FK506), an IL-2 inhibitor, prevented mitogen-stimulated IL-2 production in Jurkat cells. Treatment with PMA+IoM alone significantly increased PKC activity and the presence of BIM-I prevented PKC activation by PMA+IoM. Following 24 h treatments, the plant sterols did not affect PMA+IoM-enhanced PKC activity, cellular calcium content or calcineurin activity. Intracellular cyclic 3',5'-adenosine monophosphate (cAMP) levels were significantly reduced by PMA+IoM. The presence of FK506 prevented a PMA+IoM-induced reduction of intracellular cAMP. Likewise the plant sterols behaved in a similar manner as FK506. Our findings suggest that the suppression of IL-2 by the plant sterols was not mediated via PKC inhibition and that their effects occurred possibly via cAMP modulation and/or a calcium/calcineurin-independent pathway.

Evaluation of the anti-inflammatory efficacy of Lotus corniculatus

“…For b-sitosterol, studies have demonstrated important anti-inflammatory activity not only by inhibiting IL-12 from human Jukart T cells stimulated by concanavalin (ConA) or by phorbol-12-myristate-13-acetate plus ionomycin (PMA + IoM) (Aherne & O'Brien, 2008), but also by decreasing the eosinophil influx, mucus secretion, and IL-4/ IL-5 expression in a murine model of asthma induced by ovalbumin (Yuk et al, 2007), and the ear oedema induced by acetone in mice (Mavar-Manga et al, 2008).…”

Potential bioactive effects of casein hydrolysates on human cultured cells

“…In view of the fact that we planned to assess the effects of the casein hydrolysates on Concanavalin A (ConA)-stimulated interleukin-2 (IL-2) and interleukin-10 (IL-10) production, we chose the Jurkat T cell model for our study. Human Jurkat T cells possess membrane markers that resemble normal lymphocytes and have long served as a useful model for different immunological and other bioactivity studies (Aherne and O'Brien, 2008;Konicova et al, 1992;Luongo et al, 2003;Tanaka et al, 2005;Verlengia et al, 2004).…”

Extent of hydrolysis effects on casein hydrolysate bioactivity: Evaluation using the human Jurkat T cell line

“…The effects of casein hydrolysates on ConA-stimulated IL-2 and interleukin-10 (IL-10) production in these cells was also examined. Human Jurkat T cells were selected as they possess membrane markers that resemble normal lymphocytes and have previously been employed as a useful model for immunological and bioactivity studies (Aherne & O'Brien, 2008;Koníková, Babusíková, Kusenda, & Glasová, 1992;Luongo, Bergamo, & Rossi, 2003;Tanaka, Akaishi, Hosaka, Okamura, & Kubohara, 2005;Verlengia et al, 2004). The activity of the hydrolysates was compared with that of intact/unhydrolysed sodium caseinate (NaCN).…”