RESUMO
The mushroom Phellinus linteus (PL) has been shown to have antitumor and immunostimulatory effects. We hypothesized that the hot water extract of PL (WEPL) exerts its significant immunostimulatory effect by inducing production of the Th1-derived cytokine interferon-gamma (IFN-gamma) by T lymphocytes. T lymphocytes were isolated from the mice fed with 200 mg/kg of WEPL once a day for 4 weeks and then stimulated with the mitogen concanavaline A (Con A). IFN-gamma gene and intracellular protein expressions were analyzed by RT-PCR and flow cytometry, respectively. The production of IFN-gamma was measured by enzyme-linked immunosorbent assay. WEPL significantly enhanced the transcription of IFN-gamma mRNA. The effect of WEPL on IFN-gamma expression was further supported by a concomitant increase in the number of cells with intracellular IFN-gamma protein as well as the secretion of IFN-gamma. However, WEPL did not modulate either gene expression or protein secretion of interleukin-4, a Th2-associated cytokine, by Con A-stimulated T lymphocytes. Our results demonstrate that one of the potentially beneficial antitumor and immunostimulatory effects of WEPL may be mediated through the enhancement of IFN-gamma secretion by T lymphocytes.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Basidiomycota , Misturas Complexas/administração & dosagem , Citocinas/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Células Th1/metabolismo , Células Th2/metabolismo , Adjuvantes Imunológicos/química , Administração Oral , Animais , Basidiomycota/química , Células Cultivadas , Misturas Complexas/química , Citocinas/imunologia , Avaliação Pré-Clínica de Medicamentos , Feminino , Regulação da Expressão Gênica/imunologia , Técnicas In Vitro , Masculino , Camundongos , Células Th1/citologia , Células Th1/imunologia , Células Th2/citologia , Células Th2/imunologiaRESUMO
Cytokines produced by immune cells infiltrating pancreatic islets are important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. In this study, the effects of Fructus Benincasae Recens (FBR) extract on cytokine-induced beta-cell dysfunction were examined. Fructus Benincasae Recens extract completely protected interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma)-mediated cytotoxicity in rat insulinoma cell line (RINm5F). Incubation with FBR extract resulted in a significant reduction of IL-1beta and IFN-gamma-induced nitric oxide (NO) production, a finding that correlated well with reduced levels of the inducible form of NO synthase (iNOS) mRNA and protein. The molecular mechanism by which FBR extract inhibited iNOS gene expression appeared to involve the inhibition of NF-kappaB activation. Our results revealed the possible therapeutic value of FBR extract for the prevention of diabetes mellitus progression.