No abstract

The understanding of main mechanisms that determine the ability of immune privilege related to Sertoli cells (SCs) will provide clues for promoting a local tolerogenic environment. In this study, we evaluated the property of humoral and cellular immune response modulation provided by porcine SCs. Porcine SCs were resistant to human antibody and complement-mediated formation of the membrane attack complex (38.41±2.77% vs. 55.02±5.44%, p=0.027) and cell lysis (42.95±1.75% vs. 87.99±2.25%, p<0.001) compared to immortalized aortic endothelial cells, suggesting that porcine SCs are able to escape cellular lysis associated with complement activation by producing one or more immunoprotective factors that may be capable of inhibiting membrane attack complex formation. On the other hand, porcine SCs and their culture supernatant suppressed the up-regulation of CD40 expression (p<0.05) on DCs in the presence of LPS stimulation. These novel findings, as we know, suggest that immune modulatory effects of porcine SCs in the presence of other antigen can be obtained from the first step of antigen presentation. These might open optimistic perspectives for the use of porcine SCs in tolerance induction eliminating the need for chronic immunosuppressive drugs.

Dendropanax morbifera ( D. morbifera ), known as Dendro, means ‘omnipotent drug’ (Panax), and has been called the panacea tree. Various studies on D. morbifera are currently ongoing, aiming to determine its medicinal uses. The present study investigated the anti-inflammatory effects and underlying mechanism of a natural extract of D. morbifera leaves (DPL) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. In the present study, the following assays and models were used: MTT assay, nitric oxide (NO) assay, western blotting, ELISA and mouse models of atopic dermatitis. DPL extract markedly reduced the production of NO, inducible NO synthase and interleukin-6, as well as the nuclear translocation of nuclear factor-κB (NF-κB). Additionally, the LPS-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2), P38 and c-Jun N-terminal kinase (JNK) was suppressed by DPL extract. Taken together, these results indicate that NF-κB, ERK1/2, P38 and JNK may be potential molecular targets of DPL extract in the LPS-induced inflammatory response. Subsequently, the present study investigated the effects of DPL extract in a 2,4-dinitrochlorobenzene-induced atopic dermatitis mouse model. Ear thickness, serum immunoglobulin E levels and histological analysis revealed that the DPL extract was effective in attenuating the inflammatory response. These results indicate that DPL extract has anti-inflammatory potential and may be developed as a botanical drug to treat atopic dermatitis.

Sertoli cells (SC) are known to contain immunoprotective properties, which allow them to survive as allografts without the use of immunosuppressive drugs. Experiments were designed to determine which factors are related to prolonged survival of allogeneic SC. Balb/c derived Sertoli (TM4) and colon cancer (CT-26) cell lines were implanted beneath the kidney capsule of non-immunosuppressed C57BL/6 mice and compared their survival as allografts. Compared to TM4 graft, which survived more than 7 days after transplantation, CT-26 showed massive infiltration of polymorphonuclear cells, necrosis and enlargement of draining lymph nodes. Cultured cell lines showed no differences in their expression patterns of FasL, TGF β1, clusterin and two complement regulatory proteins (CRP, i.e., membrane cofactor protein, MCP; decay accelerating factor, DAF), but protectin (CD59), another member of CRP was expressed only on TM4. These results suggest that CD59 and unknown factors may contribute to the prolonged survival of SC in non-immunoprivileged sites.

The object of this study is to evaluate the effects of injecting adult human bone marrow stromal cells (hBMSCs) into rats with severe traumatic brain injury in acute phase and to determine more optimal injection timing between day 1 and day 2 postinjury. The lateral fluid percussion injury model was used. Adult hBMSCs were transplanted into hemisphere to injury sites in the corpus callosum ipsilateral on day 1 (n = 12) or day 7 (n = 8) after injury. A control group (n = 7) underwent only a sham operation without stem cell transplantation. Rats in all groups were analyzed by magnetic resonance spectroscopy (MRS), and by using behavioral, rotarod, and Barnes maze tests on day 1, 7, 14, and 42. Another nine randomly designated rats were sacrificed for immunohistochemical staining. Behavioral test scores increased significantly at all time-points after TBI in the day 7-injected group, compared to the others (p=0.008). GFAP staining was lower on day 42 in day 7-injected rats than in those injected on day 1. But no significant inter- or intra-group differences were observed for other tests. The injection of hBMSCs was found to have limited therapeutic potential with respect to neuroprotection after traumatic brain injury. However, because injection on day 7 after TBI produced greater functional improvements in neurobehavioral tests and more effectively suppressed astroglial activation than an injection on post-injury day 1, we cautiously recommend the injection time of day 7 post injury in hBMSCs transplantation in severe TBI, rather than day 1 post injury but further studies on developing hBMSC-based new therapeutic approaches should be warranted for improving neuroprotection in severe TBI.