These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Antiparasitic treatment of patients with P. falciparum malaria reduces the ability of patient serum to induce tissue factor by decreasing NF-kappa B activation.
    Author: Bierhaus A, Hemmer CJ, Mackman N, Kutob R, Ziegler R, Dietrich M, Nawroth PP.
    Journal: Thromb Haemost; 1995 Jan; 73(1):39-48. PubMed ID: 7740494.
    Abstract:
    Serum from patients with P. falciparum malaria at day 1 (pretherapy) induces tissue factor (TF) in cultured endothelial cells. TF induction depends on de novo transcription as shown in Nuclear Run On assays. Electrophoretic mobility shift assays demonstrated binding of AP-1 and NF-kappa B/Rel proteins to their recognition sites in the TF promotor. After therapy (day 28), stimulation of TF antigen by patient serum is reduced by 70%. When serum obtained before and after therapy was compared, a decrease of NF-kappa B activation was evident. Activation of NF-kappa B-like proteins was in part dependent on TNF alpha in patient serum, since a TNF alpha neutralizing antibody reduced induction of TF transcription and translation and induction of NF-kappa B-like proteins. Induction of TF activity was suppressed by pDTC, an inhibitor of NF-kappa B activation. When different promotor constructs of the TF gene were tested, induction was dependent upon the presence of the intact NF-kappa B-like binding site in the TF promotor. A mutant with deleted NF-kappa B, but intact AP-1 sites was not inducible. Mutation of the AP-1 sites did not prevent induction, but reduced inducibility by pretherapy serum. Therefore, NF-kappa B/Rel proteins are responsible for induction of TF transcription by pretherapy serum, but AP-1 is needed for highest inducibility. The effect of antiparasitic therapy on the induction of TF by serum from patients with complicated P. falciparum malaria is dependent on a therapy-mediated loss of activation of NF-kappa B-like proteins in post-treatment patient serum.
    [Abstract] [Full Text] [Related] [New Search]