Differential regulation of ferritin H and L subunit mRNA during inflammation and long-term iron overload

Abstract Iron overload, such as occurs in the genetic disease haemochromatosis, leads to synthesis of ferritin containing an increased proportion of L subunits. Inflammation also leads to clinically important increases in ferritin synthesis but the predominant subunit involved is unclear. Elevation of serum ferritin concentration during the acute phase response confounds its use as an indicator of body iron stores and identification of the major subunit involved may allow distinction of the ferritin associated with inflammation from that synthesized during iron overload. The present study examined H and L ferritin subunit mRNA levels in rats with: (i) longstanding iron overload, both parenteral and oral, in which changes should be maximal and stable; and (ii) inflammation of 24 and 48 h duration. A two-fold increase in L mRNA level was found in both groups of iron loaded animals while H mRNA level was unchanged. This finding would account for the observed preponderance of L subunits in ferritin during iron overload. During the course of inflammation there was a progressive decrease in L mRNA level in the liver but not the spleen. H mRNA relative to total RNA level was unchanged in both liver and spleen. It is concluded that the differential regulation of the two ferritin subunits in response to different stimuli and in different tissues occurs at the level of alteration in mRNA concentration.