POTENTIAL ANTI-TUMOR AND ANTI-INFLAMMATORY ACTIVITY OF SIX MISTLETOE PLANTS IN THE FAMILY VISCACEAE PRESENT IN WESTERN GHATS, INDIA

ABSTRACTObjectivesTo find out the cytotoxicity, anti-tumor and anti-inflammatory activities of six species of plants belongs to Viscaeceae family available in Western Ghats (India).MethodsIn vitro cytotoxicity of Viscum extracts was studied by trypan blue exclusion method and MTT assay using various cell lines. Anti-tumor activity was determined using Ehrlich ascites carcinoma (EAC) and Dalton's lymphoma ascites (DLA) cells in mice. Anti-inflammatory activities of Viscum extracts were studied using carrageenan and dextran induced mouse paw edema models in mice.ResultsAll six Viscaeceae plant extracts studied were cytotoxic towards transformed cell lines like DLA and EAC as well as to MCF-7, MDA-MB-231 and SKBR3 cell lines. V.orientale, V.nepalense and V.ramosissimum, V.trilobatum were cytotoxic towards normal cells while V.angulatum and V.capitellatum were found to be nontoxic. Excepting V.angulatum all the other species selected here showed toxicity to animals. Administration of nontoxic concentration of extracts of Viscaeceae plants significantly (P<0.001) increased the lifespan of ascites tumor bearing animals and reduced DLA cells induced solid tumor development. All these plants except V.capitallatum and V.trilobatum showed significant (P<0.001) anti-inflammatory activity against carrageenan and dextran models and reduced pro-inflammatory cytokine levels.ConclusionOut of six species studied four species of Viscum species studied were cytotoxic to tumour cells and inhibited tumour development. Of the six species studied V. angulatum was non-toxic to animals and showed maximum efficiency as an antitumour agent. These plants showed significant anti-inflammatory activity and reduced inflammatory markers

A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio