Asthma transcription factors

Munthe-Kaas MC, Carlsen KH. Haland G. Devula-palli CS, Gervin K, Egeland T. Carlsen KL. Undlien D T cell-specific T-box transcription factor haplo-type is associated with allergic asthma in childrea J Allergy Chn Immunol 2008 121 51 -56. 

Inhaled corticosteroids mediate a variety of immunological actions and are commonly used in the treatment of allergic asthma [28]. However, not all patients respond well to this treatment and some are steroid-resistant. In a recent study, Tantisira et al. [29] described a new genetic non-synonymous variation in TBX21 that encodes for the transcription factor T-bet (T-box expressed in T cells) associated with significant improvement of the airway hyperresponsiveness in children affected by allergic asthma [30]. Noteworthy, the... 

GR inhibitory interaction with T-bet may be an important mechanism underlying the immunosuppressive properties of GCs [27]. It is therefore important to determine the footprint of T-cell-specific transcription factor expression and binding on the IFN-y promoter in asthmatics, resulting in a closer classification of this disease. Allergic asthma is possibly a multifaceted disease that can be further better subclassified and therefore treated with different strategies. 

Nuclear factor kappa B (NF-kB) serves as a central regulator of the human immune and inflammatory response, and is a family of inducible transcription factors found virtually ubiquitously in all cells and functions in a variety of human diseases including those related to inflammation, cancer, asthma, atherosclerosis, AIDS, septic shock, and arthritis. Due to its role in a wide variety of diseases, NF-kB has become one of the major targets for drug development. Inhibition of NF-kB activity potentially contributes to cancer chemoprevention [27,28]. 

Knock-out mice, for a transcription factor T-bet (required for Thl-cell synthesis), make fewer Thl and more Th2 cells, and suffer the lung changes typical of human asthma, even though they are not exposed to any particnlar allergen. 

NF-kB comprises a family of inducible transcription factors that serve as relevant mediators of the inflammatory response. This factor is also involved in protecting cells from undergoing apoptosis in response to DNA damage or treatment with cytokine [89]. Normally, NF-kB is kept inactive by a cytoplasmic inhibitor of kB (IkB) proteins, which are phosphorylated by a cellular kinase complex known as IKK, made up of two kinases, IKK-a and IKK-p. The phosphorylation of IkB by these kinases leads to the degradation of the proteins and to the translocation of NF-kB to the nucleus. Once in the nucleus, NF-kB activates gene expression of cells exposed to growth factors and cytokines [90,91]. Activation of the NF-kB pathway is thus involved in the pathogenesis of chronic inflammatory diseases such as rheumatoid arthritis and asthma... 

---