(Molecular Biology Thematic Programme of Semmelweis University)
Szakterületek:
Általános- és belgyógyászat
Endothelial cells play an important role in sensing danger signals and regulating
inflammation. Several factors are capable of inducing a proinflammatory response (e.g.,
LPS, histamine, IFNγ, and bradykinin), and these factors act simultaneously during
the natural course of the inflammatory reaction. We have previously shown that the
complement protein mannan-binding lectin-associated serine protease-1 (MASP-1) also
induces a proinflammatory activation of the endothelial cells. Our aim was to investigate
the possible cooperation between MASP-1 and other proinflammatory mediators when they
are present in low doses. We used HUVECs and measured Ca2+ mobilization, IL-8, E-selectin,
VCAM-1 expression, endothelial permeability, and mRNA levels of specific receptors.
LPS pretreatment increased the expression of PAR2, a MASP-1 receptor, and furthermore,
MASP-1 and LPS enhanced each other’s effects in regulating IL-8, E-selectin, Ca2+
mobilization, and changes in permeability in a variety of ways. Cotreatment of MASP-1
and IFNγ increased the IL-8 expression of HUVECs. MASP-1 induced bradykinin and histamine
receptor expression, and consequently, increased Ca2+ mobilization was found. Pretreatment
with IFNγ enhanced MASP-1-induced Ca2+ mobilization. Our findings highlight that well-known
proinflammatory mediators and MASP-1, even at low effective doses, can strongly synergize
to enhance the inflammatory response of endothelial cells.