Pin1 protein regulates Smad protein signaling and pulmonary fibrosis.

Interstitial pulmonary fibrosis is caused by the excess production of extracellular matrix (ECM) by Fb in response to TGF-β1. Here, we show that the peptidyl-prolyl isomerase Pin1 modulates the production of many pro- and antifibrogenic cytokines and ECM. After acute, bleomycin injury, Pin1(-/-) mice showed reduced, pulmonary expression of collagens, tissue inhibitors of metalloproteinases, and fibrogenic cytokines but increased matrix metalloproteinases, compared with WT mice, despite similar levels of inflammation.

Transforming Growth Factor-1 Antagonizes Interleukin-5 Pro-Survival Signaling by Activating Calpain-1 in Primary Human Eosinophils.

Background: Eosinophils rapidly undergo apoptosis unless exposed to prosurvival cytokines such as interleukin 5 (IL-5) or granulocyte-macrophage colony stimulating factor (GM-CSF). eosinophils are exposed to TGF-β 1 which can induce apoptosis suggesting it may function to counteract the effects of IL-5 or GM-CSF and limit, tissue eosinophilia.

Objective: The objective of this study was to investigate the proapoptotic effects of TGF-β alone and in combination with IL-5 on eosinophils.

Loss of the innate immunity negative regulator IRAK-M leads to enhanced host immune defense against tumor growth.

IRAK-M is a negative regulator of innate immunity signaling processes. Although attenuation of innate immunity may help to prevent excessive inflammation, it may also lead to compromised immune surveillance of tumor cells and contribute to tumor formation and growth. Here, we demonstrate that IRAK-M(-/-) mice are resistant to tumor growth upon inoculation with transplantable tumor cells.

Differential regulation and role of interleukin-1 receptor associated kinase-M in innate immunity signaling.

Toll-like-receptor mediated signaling is finely regulated by a complex intracellular protein network including the interleukin-1 receptor associate kinases (IRAKs). IRAK-4, 1, and 2 may positively regulate innate immunity signaling through the activation of various downstream kinases such as MAPKs. In contrast, IRAK-M plays an inhibitory role through unknown mechanism.

DNA prime followed by protein boost enhances neutralization and Th1 type immunity against FMDV.

Prime-boost strategy has been exhibited its potency to enhance immune responses, which would be important to the success to develop a vaccine against the foot-and-mouth disease virus (FMDV). An eukaryotic expression construct encoding the FMDV capsid VP1 protein with a recombinant VP1 protein or a commercial FMDV vaccine were tested in the prime-boost strategy in mice and cattle trials. The levels of induced specific antibodies, T cell proliferations, and DTH activities were significantly higher in the prime-boost groups than in those vaccinated with DNA, protein or FMDV vaccine alone.

The adjuvant effect of levamisole on killed viral vaccines.

To explore adjuvants that are capable of promoting Th1-biased immune response, we investigated the usefulness of levamisole (LMS) as one such adjuvant for two different preparations of killed viral vaccines, derived from the foot mouth disease virus (FMDV) or the porcine respiratory reproductive syndrome virus (PRRSV) and tested respectively in BALB/c or C57 BL/6 mice. The results showed that LMS induced different types of immune responses in the host, depending on its dosage. While a high level of serum IgG was induced by using LMS at 2%, the most robust T cell proliferation was induced with LMS at 0.

Induction of active immune suppression by co-immunization with DNA- and protein-based vaccines.

Although immunization has been used for eliciting immune response, here we show that it can also induce immune suppression. When a DNA vaccine encoding a viral antigen such as the VP1 protein from the foot and mouth disease virus is administered together with its recombinant protein antigen or a viral preparation containing the same antigen, the immunized animals developed significantly reduced antigen-specific T cell-mediated responses and became impaired to subsequent rechallenge with the same antigen. The induction of immune suppression is mediated by suppressor T cells, as demonstrated by an adoptive transfer experiment and mixed lymphocyte reactions.

Induction of Th1 type response by DNA vaccinations with N, M, and E genes against SARS-CoV in mice.

Vaccination against the SARS-CoV infection is an attractive means to control the spread of viruses in public. In this study, we employed a DNA vaccine technology with the levamisole, our newly discovered chemical adjuvant, to generate Th1 type of response. To avoid the enhancement antibody issue, genes encoding the nucleocapsid, membrane, and envelope protein of SARS-CoV were cloned and their expressions in mammalian cells were determined.