Selective regulation of nuclear orphan receptors 4A by @entity859 receptor subtypes in XXXX mast cells.

@entity1 @entity32 @entity19350 @entity859 @entity4515 @entity18203 @entity40803 @entity16629 @entity15997 @entity8744 @entity6164 @entity1366 @entity5282
Nuclear orphan receptors 4A (NR4A) are early responsive genes that belong to the superfamily of hormone receptors and comprise @entity5282 , @entity18203 and @entity40803 . They have been associated to transcriptional activation of multiple genes involved in @entity32 , apoptosis and cell cycle control. Here, we establish a link between NR4As and @entity859 , a paradoxical inflammatory molecule that can contribute to persistence of @entity32 or mediate inflammatory shutdown. Transcriptomics screening of the @entity1 mast cell-line HMC-1 revealed a sharp induction of transcriptionally active @entity18203 and @entity40803 by the @entity859 analogue @entity19350 . The concomitant treatment of NECA and the @entity859 receptor A(2A) (A(2A)AR) selective antagonist @entity8744 exaggerated this effect, suggesting that upregulation of these factors in mast cells is mediated by other AR subtypes (A(2B) and A(3)) and that A(2A)AR activation counteracts @entity18203 and @entity40803 induction. In agreement with this, A(2A)AR-silencing amplified NR4A induction by NECA. Interestingly, a similar A(2A)AR modulatory effect was observed on @entity1366 phosphorylation because A(2A)AR blockage exacerbated NECA-mediated phosphorylation of @entity1366 . In addition, @entity6164 or @entity16629 inhibition prevented @entity1366 phosphorylation and antagonized AR-mediated induction of @entity18203 and @entity40803 , suggesting the involvement of these kinases in AR to NR4A signaling. Finally, we observed that selective A(2A)AR activation with @entity15997 blocked @entity4515 -induced @entity1366 phosphorylation and modulated the overexpression of functional nuclear orphan receptors 4A. Taken together, these results establish a novel @entity6164 /ERK/nuclear orphan receptors 4A axis for adenosinergic signaling in mast cells, which can be modulated by A(2A)AR activation, not only in the context of @entity859 but of other mast cell activating stimuli as well.
