TH2 Cytokines and Associated Transcription Factors as Therapeutic Targets in Asthma

Yutaka      Nakamura; Makoto      Hoshino

Abstract

The increasing levels of morbidity and mortality due to the rising prevalence of asthma and other allergic diseases have inspired investigations of several new molecular techniques to improve treatment. Recently, several preclinical studies have been published which utilize attributes or facets of DNA to address asthma therapy. These novel therapeutics include antisense oligonucleotides against TH2 cytokines and associated transcription factors. While no clinical experience has yet been reported for any of these areas of research in asthma, specific small molecule inhibitors of TH2 cell responses would be desirable for treatment of this chronic disease. Six transcription factors (c- Maf, NF-AT, NF-IL-6, AP-1, STAT-6 and GATA-3) have been implicated in the differentiation of TH2-type lymphocytes and therefore, in addition to TH2-type cytokines, represent therapeutic targets for asthma. This review will focus on new research involving suppression of Th2-type cytokines and associated transcription factors using antisense and decoy oligonucleotides. Recently, novel oligonucleotides have been devised to improve stability in vitro and in vivo stability against nucleases, and the efficacy of these approaches will also be presented.

Keywords: chronic inflammatory disease, bronchoconstrictor, cytokine, antisense oligodeoxynucleotides, rna transcript, antisense dna, allergic diseases, chemokines, th lymphocytes