'Polskie Towarzystwo Biochemiczne (Polish Biochemical Society)'
Abstract
NALP1 (also called DEFCAP, NAC, CARD7) has been shown
to play a central role in the activation of inflammatory caspases
and processing of pro-IL1β (pro-interleukin-1β). Previous studies
showed that NALP1 is highly expressed in peripheral blood
mononuclear cells. In the present study, we report that expression
of NALP1 is absent from CD34+ haematopoietic blast cells,
and its levels are upregulated upon differentiation of CD34+
cells into granulocytes and to a lesser extent into monocytes.
In peripheral blood cells, the highest levels of NALP1 were
observed in CD3+ (T-lymphocytes), CD15+ (granulocytes) and
CD14+ (monocytes) cell populations. Notably, the expression of
NALP1 was significantly increased in the bone marrow blast
cell population of some patients with acute leukaemia, but not
among tissue samples from thyroid and renal cancer. A search for
consensus sites within the NALP1 promoter revealed a sequence
for CREB (cAMP-response-element-binding protein) that was
required for transcriptional activity. Moreover, treatment of TF1
myeloid leukaemia cells with protein kinase C and protein kinase
A activators induced CREB phosphorylation and upregulated
the mRNA and protein levels of NALP1. Conversely, ectopic
expression of a dominant negative form of CREB in TF1 cells
blocked the transcriptional activity of the NALP1 promoter and
significantly reduced the expression of NALP1. Thus NALP1
is transcriptionally regulated by CREB in myeloid cells, a
mechanism that may contribute to modulate the response of these
cells to pro-inflammatory stimuli