Genetic immune modulation of Ran GTPase against different microbial pathogens.

Septic shock characterized by pro-inflammatory cytokine storm can be induced by a variety of microbial infections. Typical pro-inflammatory cytokines include TNFalpha, IL1 and IL6. Although one or more of them is often expressed in any given microbial infection, usually it is the elevation of one cytokine that becomes predominant at a particular time in a given infection.

Presence of prepackaged mRNA in virions of DNA adenovirus.

Ran GTPase has been shown to be involved in host innate immune response, and two alleles, RanT/n and RanC/d, which differ from each other by a single nucleotide, have opposite effects on host innate immune response. In this study, we showed that although intravenous administration in mice with either Ran cDNA using an identical adenovirus (Ad) vector resulted in no significant difference in vector tissue distribution, intraperitoneal administration resulted in effective vector transduction into peritoneal macrophages, coupled with a striking difference in vector tissue distribution in 2 h or less. We further demonstrated the presence of prepackaged RNA in virions of Ad vectors, in cells actively producing Ad virus particles, and in cells very shortly after Ad infection.

A functional connection between RanGTP, NF-kappaB and septic shock.

RanGTPase is importantly involved in diverse biological functions, such as nuclear transport, spindle formation during mitosis, DNA replication and cell division. This review summarizes yet another new role of Ran - control of the activity of NF-kappaB in host immune responses. Overexpression of a specific allele of Ran results in preferential accumulation of nuclear RanGTP, downmodulation of proinflammatroy cytokine production and protection against septic shock.