Naslov
Regulation of aminopeptidase N (EC 3.4.11.2 ; APN ; CD13) on the HL-60 cell line by TGF-β1

Autori
Gabrilovac, Jelka ; Breljak, Davorka ; Čupić, Barbara

Izvornik
International immunopharmacology (1567-5769) 8 (2008), 5; 613-623

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Aminopeptidase N ; Ca++ signaling ; CD13 ; IFN-γ ; Myelo-monocytic HL-60 cell line ; TGF-β 1

Sažetak
Membrane-bound peptidases interfere with cellular growth, differentiation, activation and death by fine-tuning local concentrations of various signaling peptides such as the growth factors, hormones, chemokines and cytokines. We examined the effects of anti-inflammatory cytokine transforming growth factor-beta1 (TGF-β1) on the expression and activity of aminopeptidase N (APN), an ectoenzyme processing several signaling peptides. Myelo-monocytic HL-60 cell line having high basal APN activity corresponding to the membrane CD13 marker served as a model. Regulation of CD13/APN was assayed at the levels of mRNA and at the membrane marker CD13. Functional properties of CD13/APN were examined by measuring the enzyme activity, and the signal transduction ability, followed as Ca++ mobilization triggered by APN-blocking WM-15 antibody. TGF-β1 at physiological concentrations (0.16 to 2.5 ng/mL) increased expression of CD13 both at mRNA and membrane protein level in a time- and concentration-dependent manner. Transcriptional activation of CD13 by TGF-β1 is suggested as actinomycin-D, an inhibitor of RNA synthesis, abrogated the TGF-β1-induced up-regulation of CD13. Increased membrane CD13 expression was associated with an increase of its enzyme (APN) activity and with a decrease of its signal transduction ability. Anti-inflammatory cytokine TGF-β1 counteracted the effects of pro-inflammatory cytokine IFN-γ on membrane CD13 expression in a time- and concentration-dependent fashion, suggesting a cytokine-regulated role of CD13/APN in inflammation. This is the first report on regulation of CD13/APN expression by TGF-β1 on immature cells of myelo-monocytic origin. As obtained with physiological concentrations of TGF-β1 these findings may be relevant for cytokine-regulated CD13/APN expression on mature myeloid cells in the course of inflammation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA