Leishmanial lipid suppresses tumor necrosis factor α, interleukin‐1β, and nitric oxide production by adherent synovial fluid mononuclear cells in rheumatoid arthritis patients and induces apoptosis through the mitochondrial‐mediated pathway

Abstract

Results. Leishmanial lipid inhibited the release of tumor necrosis factor ␣, interleukin-1␤, and NO in the culture, decreased their cytosolic protein levels, and decreased NF-B p65 levels in SFMCs, in a dosedependent manner. It had the reverse effect on interleukin-10 levels. Leishmanial lipid-induced apoptosis involved the activation of caspase 3, caspase 9, and Bax, the release of cytochrome c, the alteration of mitochondrial membrane potential, and the downregulation of Bcl-2.Conclusion. These results suggest that leishmanial lipid has strong antiinflammatory and apoptosisinducing effects on SFMCs from patients with RA, and that apoptosis occurs via the mitochondrial pathway.

Leishmanial sphingolipid induces apoptosis in Sarcoma 180 cancer cells through regulation of tumour growth via angiogenic switchover

“…We are also developing a new entity, i.e. leishmanial lipid, which has already been reported to have apoptosis-inducing effect in synovial cells isolated from rheumatoid arthritis patients [15]. Recently, we have reported the protective role of this lipid against Escherichia coli-induced bacterial sepsis [14].…”

“…We very recently reported that the leishmanial lipid shows biological activity in in vitro and in vivo systems and also proves useful for rheumatoid arthritis patients through immune regulation [14,15]. So, we have decided to find out if the sphingolipid isolated from Leishmania donovani can also fight against cancer by inducing apoptosis with simultaneous regulation of angiogenesis and inflammatory situation in in vivo systems.…”

Lipid Isolated from aLeishmania donovaniStrain ReducesEscherichia coliInduced Sepsis in Mice through Inhibition of Inflammatory Responses

“…TLC was performed in chloroform-methanol-water (90/10/1) and lipid spots were visualized using iodine spray [22]. …”

“…Aliquots of the supernatant containing nuclear protein were added to incubation wells precoated with the NF- κ B p65 DNA-binding consensus sequence, and the translocated p65 subunit present in nuclear lysate was assayed [22]. …”

“…It was reported that leishmanial lipids possess biological activity against stimulated macrophages and mammalian lymphocytes [21]. Recently we have shown that lipid from an attenuated strain of Leishmania donovani promastigote (MHO/IN/1978/UR6) suppresses several inflammatory mediators by inducing apoptosis in adherent synovial fluid mononuclear cells (SFMCs) of rheumatoid arthritis patients [22]. These findings encouraged us to evaluate the anti-inflammatory role of the leishmanial lipid against gram-negative bacteria ( E. coli ) induced inflammatory progression towards acute pulmonary damage.…”