Hjv deficiency abrogates hepcidin-dependent ferroportin internalization and hypoferremic response to acute inflammation. Five-week-old male wild-type (wt), Hfe^−/−, Hjv^−/−, and double Hfe^−/−Hjv^−/− mice (all in C57BL/6 background; n = 6 for each experimental group) were injected with either phosphate-buffered saline or 1 μg/g LPS. After 4 hours, all animals were sacrificed; sera were used for iron biochemistry, and tissues were processed for preparation of RNA and protein extracts or fixed for histology. (A) Serum iron; (B) transferrin saturation; (C) TIBC; (D) qPCR analysis of liver Hamp mRNA; (E) serum hepcidin; (F) qPCR analysis of liver ferroportin (Fpn + IRE) mRNA (IRE-containing isoform). All data are presented as the mean plus or minus SEM. Statistical analysis was performed by 2-way ANOVA. Statistically significant differences (P < .05) across genotypes (vs columns a, b, c, a′, b′) are indicated by a, b, c, a′, b′, and across LPS treatment by the pound sign (#). (G) Immunohistochemical staining of ferroportin in liver sections (original magnification ×20 and ×40). Arrows indicate ferroportin internalization in Kupffer cells from LPS-treated wt and Hfe^−/− mice.