p38 MAPK signaling during murine preimplantation development.

Mitogen-activated protein kinase (MAPK) pathways mediate some important cellular processes and are likely to also regulate preimplantation development. The role of p38 MAP kinase signaling during murine preimplantation development was investigated in the present study. p38 MAPK, p38-regulated or -activated kinase (PRAK; MK5), map kinase-activated protein kinase 2 (MK2), and heat shock protein 25 (hsp25) mRNAs and proteins were detected throughout preimplantation development. Two-cell stage embryos cultured in the presence of SB220025 and SB203580 (specific inhibitors of p38 MAPK alpha/beta), progressed to the eight-cell stage with the same frequency as controls; however, treated embryos halted their development at the 8- to 16-cell stage. In addition, embryos treated with p38 MAPK inhibitors displayed a complete loss of MK2 and hsp25 phosphorylation and also a complete loss of filamentous actin as indicated by the absence of rhodamine-phalloidin staining. In these inhibitor-treated groups, the embryos were composed of a mixture of compacting and noncompacting cells, and the embryos were one to two cell divisions behind controls. Treated embryos remained viable as the developmental blockade was rescued by removing embryos from the drug treatment and placing them in drug-free medium until they progressed to the blastocyst stage. This study demonstrates that p38 MAPK activity is required to support development through the murine preimplantation interval

DYNAMIC RESPONSE OF FLUID FLOW THROUGH STRAIGHT AND CURVED LINES

Abstract not availabl

An anti-inflammatory role for gamma delta T lymphocytes in acquired immunity to Mycobacterium tuberculosis.

Although a role for gammadelta receptor-bearing T cells in the acquired immune response to infection with Mycobacterium tuberculosis is suggested by several lines of evidence, the only data indicating a possible role in specific protective immunity have been provided by very high dose i.v. infection models. In the current study, more modest low dose inocula delivered by the aerosol route grew identically in wild-type controls and in mutant mice in which the Cdelta gene of the gammadelta TCR has been disrupted by homologous recombination. This situation did not change if the inoculum size was increased or if an aerosol challenge with an M. tuberculosis strain of higher virulence was given. However, while the control and containment of these infections was similar, the mutant mice exhibited a substantial pyogenic form of the granulomatous response compared with the lymphocytic response seen in control animals, a finding that may well explain mortality in the former group if high i.v. doses are given. These data indicate that gammadelta T cells do not directly contribute to protection against tuberculosis or that they do so only when bacterial loads are very high. Instead, the data suggest that gammadelta T cells perhaps play an important role by influencing local cellular traffic, promoting the influx of lymphocytes and monocytes, and limiting the access of inflammatory cells that do not contribute to protection but may cause tissue damage

Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis.

&lt;p&gt;In this study, the hsp60 and hsp70 heat shock protein antigens of Mycobacterium tuberculosis were tested as potential vaccine candidates, using purified recombinant protein antigens or antigens encoded in the form of a DNA plasmid vaccine. Guinea pigs vaccinated with a mixture of the two proteins showed no evidence of resistance to low-dose aerosol challenge infection and quickly developed severe lung damage characterized by necrotizing bronchointerstitial pneumonia and bronchiolitis. As a result, we turned instead to a DNA vaccination approach using a plasmid encoding the hsp60 antigen of M. tuberculosis. Although immunogenic in mice, vaccination with plasmid DNA encoding hsp60 was not protective in that model or in the guinea pig model and again gave rise to similar severe lung damage. This study seriously questions the safety of vaccines against tuberculosis that target highly conserved heat shock proteins.&lt;/p&gt;</p

Forum : Vol. 33, No. 02 (Summer : 2009)

https://digitalcommons.usf.edu/forum_magazine/1047/thumbnail.jp