Trichostatin A attenuates airway inflammation in mouse asthma model

Abstract

TSA attenuated the development of allergic airway inflammation by decreasing expression of the Th2 cytokines, IL-4 and IL-5, and IgE, which resulted from reduced T cell infiltration. Our results suggest that HDAC inhibition may attenuate the development of asthma by a T cell suppressive effect.

Conserved responses to trichostatin A in rodent lungs exposed to endotoxin or stretch

“…In contrast, comprehensive evidence from experiments with isolated lungs and those with intact animals suggest that on the protein level the overall effect of TSA in vivo tends to be anti-inflammatory. This conclusion is corroborated by the antiinflammatory action of HDACi in experimental models of acute lung injury (this study), asthma [20], sepsis [21], arthritis [22,38], autoimmune encephalomyelitis [39], colitis [40] and concanavalin-A-induced hepatitis [21]. From the present study we suggest that the discrepancies between the in vivo and perfused lung studies on the one hand, and the cell culture studies on the other may be ascribed to the focus on M A N U S C R I P T has not revealed a pattern that correlated with the current findings (data not shown).…”

“…HDACi have been suggested as drugs for the treatment of several inflammatory disorders including asthma, COPD, lupus erythematosus or arthritis [3,4,20,44,45], as well as cancer [2]. Given the contradictory effects of TSA and other HDACi on the expression of many genes, their use as potential drugs is expected to have difficultto-predict effects and side effects.…”

“…On the other hand, in vivo TSA reduced rather than enhanced the expression of IL-4, IL-5 and immunoglobulin E in an asthma model [20]. In addition, in other animal models of inflammation HDACi reduced the endotoxin-induced serum levels of TNF, IL-1, IL-6 and IFNγ in a sepsis model [21] and IL-6 and IL-1β levels in an arthritis M A N U S C R I P T…”

Histone Deacetylase Inhibitors Suppress TF-κB-dependent Agonist-driven Tissue Factor Expression in Endothelial Cells and Monocytes

“…We found that Յ1 M TSA has no significant effect on the viability of HUVEC as detected by trypan blue staining after a 24-h treatment (data not shown). For our studies, we chose doses and treatment times similar to those previously used successfully to investigate the influence of TSA on endothelial NO synthase expression and angiogenesis in HUVEC in vitro (15,32) and some inflammatory disease models in vivo (18,32).…”

Histone Deacetylase Inhibitors Modulate Interleukin 6-dependent CD4+ T Cell Polarization in Vitro and in Vivo

“…These results were complemented in vivo by investigating inflammatory models such as concanavalin A-induced hepatitis or LPS-induced shock in mice (7). Following these initial data, the anti-inflammatory potency could be confirmed in models of nephritis (8), arthritis (9), intestinal inflammation (6,10), graft versus host disease (11), and asthma (12). In addition, the HDAC inhibitor ITF2357 has shown clinical efficacy in clinical trials for juvenile arthritis (13).…”