RT Journal Article
SR Electronic
T1 IL6 mediated proliferative responses in human pulmonary vascular cells (PVCs) are differentially modulated by iron/heme/hemoglobin
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P5152
VO 42
IS Suppl 57
A1 Latha Ramakrishnan
A1 Sharon Mumby
A1 Chao Meng
A1 S. John Wort
A1 Gregory Quinlan
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P5152.abstract
AB Pulmonary Arterial Hypertension (PAH) is characterised by progressive pulmonary vascular remodelling culminating in heart failure. Disrupted iron metabolism and anaemia have been linked to development of PAH suggesting iron supplementation may be beneficial. However iron compounds are known proliferative agents. IL6 which is both proinflammatory and central to iron homeostasis is elevated in PAH. With emerging evidence of minor hemolysis in PAH patients, the availability of heme and/or haemoglobin (Hb) to PVCs may further impact on cellular responses. We aim to address the above issues in this study.Human pulmonary arterial smooth muscle cells (PASMCs) & endothelial cells (PAECs) were exposed to iron (FAC)/Heme/Hb prior to treatment with IL6. Cell proliferation was quantified by Cyquant. RTPCR for expression of Hepcidin (regulatory hormone), Ferroportin (exporter), HO1, CD163(Hb scavenger) was also performed.IL6 alone caused proliferation reversed by iron in PASMCs but not in PAECs. Heme restricted while Hb supported proliferation in both cell types. Basal CD163 mRNA was undetectable in PAECs but induced by IL-6. Hepcidin, Ferroportin and HO1 were also contrastingly regulated by IL6.View this table:Thus PVCs respond distinctly to the IL6 stimulus which is further modulated by the availability of Iron/Heme/Hb. Besides IL-6 differentially regulated mRNA expression of genes involved in iron homeostasis. Further investigation of iron handling in PVCs seems warranted.