FIG. 1.

H₂S suppresses LPS-induced hepcidin production and regulates iron homeostasis in mice. C57BL/6 and C3H mice were preinjected with NaHS for 3 days (i.p., 6 mg/kg/day), followed by LPS (0.5 mg/kg), as stated in the Materials and Methods section. C57BL/6 and C3H mice were killed after 6 and 24 h, respectively. (A, B) NaHS treatment attenuated LPS-induced hepatic Hamp mRNA expression (A) and serum hepcidin levels (B) in C57BL/6 mice (n=6). (C) Representative immunoblots revealed that hepatic ferroportin (FPN) protein levels in C57BL/6 mice were decreased by LPS challenge, but reversed by NaHS. Densitometry analysis is indicated below the blots (n=6). (D) Plasma iron concentrations in different groups of C57BL/6 mice (n=6). (E, F) NaHS ameliorated splenic iron accumulation induced by LPS in C3H mice 24 h after LPS challenge (n=6). The formation of Prussian blue is indicated by solid arrows in the representative images. (G) The serum IL-6 level of C57BL/6 mice was dramatically induced after LPS challenge and effectively reduced by NaHS (n=6). (H) Changes in hepatic JAK2/STAT3 activation were consistent with serum IL-6 level (n=6). GAPDH served as the loading control. Representative immunoblots and images are presented with densitometry analysis in the Supplementary Data. Data are presented as the mean±SEM. ^#p<0.05, ^##p<0.01, and ^###p<0.001, all compared with the control group; *p<0.05 and **p<0.01 compared with the LPS group. GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IL-6, interleukin-6; JAK2, Janus kinase 2; LPS, lipopolysaccharide; STAT3, signal transducer and activator of transcription 3. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars