Gedunin, a natural tetranortriterpenoid, modulates T lymphocyte responses and ameliorates allergic inflammation

Abstract

T lymphocytes are critical cells involved in allergy. Here, we report that the natural tetranortriterpenoid gedunin impaired allergic responses primarily by modulating T lymphocyte functions. The intraperitoneal (i.p.) administration of gedunin inhibited pleural leukocyte accumulation triggered by intra-pleural (i.pl.) challenge with ovalbumin (OVA) in previously sensitized C57BL/6 mice; this inhibition was primarily due to the impairment of eosinophil and T lymphocyte influx. Likewise, i.pl. pre-treatment with gedunin inhibited eosinophil and T lymphocyte migration into mouse lungs 24 h after OVA intra-nasal (i.n.) instillation. Pre-treatment with gedunin diminished the levels of CCL2, CCL3, CCL5, CCL11, Interleukin-5 and leukotriene B(4) at the allergic site. In vitro pre-treatment with gedunin failed to inhibit T lymphocyte adhesion and chemotaxis towards pleural washes recovered from OVA-challenged mice, suggesting that gedunin inhibits T lymphocyte migration in vivo via the inhibition of chemotactic mediators in situ. In vivo pre-treatment with gedunin reduced the numbers of CD69(+) and CD25(+) T lymphocytes in the pleura and CD25(+) cells in the thoracic lymph nodes 24 h after OVA i.pl. challenge. In accordance, in vitro treatment of T lymphocytes with gedunin inhibited α-CD3 mAb-induced expression of CD69 and CD25, proliferation, Interleukin-2 production and nuclear translocation of NFκB and NFAT. Notably, post-treatment of mice with gedunin reverted OVA-induced lung allergic inflammation by decreasing the T lymphocyte and eosinophil counts and the levels of eosinophilotactic mediators in bronchoalveolar lavage fluid. Our results demonstrate a remarkable anti-allergic effect of gedunin due to its capability to modulate T cell activation and trafficking into the airways.

Impact of Methimazole Treatment on Magnesium Concentration and Lymphocytes Activation in Adolescents with Graves’ Disease

“…CD69 represents one of the earliest activation markers of T lymphocytes appearing within 1–2 h after stimulation [47, 48]. Consequently, CD69 expression has been used as a marker of T cell activation both in vivo and in vitro [49–51]. Over-expression of both CD25 and CD69 antigens in the outer membrane are observed in lymphocytes from patients with autoimmune diseases, probably as a mirror image of the immune system activation.…”

The effect of andiroba oil and chitosan concentration on the physical properties of chitosan emulsion film

“…Andiroba oil also contains triterpenes, tetraterpenes, alkaloids, and glycerides [9] . Andiroba seed oil is currently considered to be acaricides [10] , larvicidal against Aedes aegypti [11] , as well as being an antiplasmodial [5] , anti-inflammatory [12] , anti-allergic [7,13,14] , and also suitable for wound healing [3,4] . The ethanolic extract of Carapa guianensis leaves was evaluated for antibacterial and wound healing activity, using excision, incision, and dead space wound models in rats.…”

Gedunin Binds to Myeloid Differentiation Protein 2 and Impairs Lipopolysaccharide-Induced Toll-Like Receptor 4 Signaling in Macrophages

“…Gedunin and its analogs are an important bioactive limonoid-type tetranortriterpene isolated from the Meliaceae family and are reported to display a wide range of biologic activities, including antitumor, antimalarial, antiallergic, and anti-inflammatory activity in different experimental models (Brandt et al, 2008;Kamath et al, 2009;Ferraris et al, 2011Ferraris et al, , 2012Miranda Júnior et al, 2012;Henriques and Penido, 2014;Conte et al, 2015). The molecular mechanism of action related to the biologic effects of gedunin relies on the inhibition of Hsp90 activity via specific binding to the cochaperone p23 and by disrupting the cochaperone Cdc37-Hsp90 interaction (Matts et al, 2011;Patwardhan et al, 2013).…”