Due in part to their ability to orchestrate downstream inflammatory responses that lead to joint damage and disease progression, pathogenic expansions of T and B lymphocytes are appreciated to play key roles in the pathogenesis of rheumatoid arthritis.
However, it is presumed that increased H2O2 levels could be perceived directly by redox-sensitive transcription factors (TFs) that orchestrate downstream cascades (Miller et al. 2008).
But that is just a "downstream" measure.
A recent study demonstrates that IL-4 orchestrates downstream signaling via the IL-4Rα/JAK1/STAT3/STAT6 IL-4Rα/JAK1/STAT3/STAT6lizes both IL-4Rα/JaxisSTAT3 and IL-13Rα1/Tyk2/STAT1/STAT6 signaling cascades to regulate expression of the target genes [ 48].
While neutrophils have traditionally been regarded as professional phagocytes which clear debris and bacterial pathogens and delay healing, evidence is emerging to support a much wider role in orchestrating downstream events (Weiss, 1989; Nathan, 2006; Bastian et al, 2011).
In the mammalian MMR system, the heterodimeric complexes MSH2-MSH3/MSH6 (MutS) recognize mispaired bases and insertion-deletion loops and then the MLH1-PMS2 coMutLx (MutL) interacts with MutS and orchestrates downstream DNA repair events [ 10].
These events in turn orchestrate specific downstream responses.
Moreover, considering the role of bronchial epithelial cells in orchestrating various downstream responses to CS [ 20], drugs targeting KL deficiency in the cells may improve excessive inflammation and oxidative injury without the need for separate therapies.
The most important finding of this systematic RPPA analysis is the identification of PKC as a key player that orchestrates the downstream signaling pathways regulating apoptosis and cell survival.
They have the power to obstruct policies, stir up controversies and orchestrate pressure to kill measures they don't like.
The mechanisms that decipher the protein folding status and orchestrate a coordinated downstream response, either adaptation or apoptosis, are fundamentally significant, unknown, and require further investigation.
