HEPATIC AND EXTRAHEPATIC TRANSCRIPTION OF INTER-ALPHA-INHIBITOR FAMILY GENES UNDER NORMAL OR ACUTE INFLAMMATORY CONDITIONS IN RAT

The expression and level of the mRNAs for the five genes that code for a set of plasma proteins collectively referred to as the inter-alpha- inhibitor family have been studied in rat under a normal condition or in the course of a turpentine-induced, systemic inflammation. In healt hy rats, all five mRNAs [H1, H2, H3, H4, and alpha 1-microglobulin/bik unin precursor (AMBP)] are expressed primarily in liver and two of the m (H2 and H3) are found to a lower extent in brain. By in situ hybridi zation onto sections of a normal brain, the H3 mRNA has been precisely localized to the hypothalamus, amygdala, pontine area, optic tectum, and cerebellum. By reverse transcriptase-polymerase chain reaction of total RNAs obtained from a panel of organs, low amounts of one or more mRNA(s) could be detected in other locations (e.g., intestine and sto mach). Furthermore, the extrahepatic expressions of several of these g enes are up- or downregulated at 20 h after the start of a turpentine- induced inflammation. In liver, the contents of H3 and H4 mRNA are upr egulated, whereas those of AMBP and H2 are downregulated during the ac ute phase. This is accounted for by changes in gene transcription, the kinetics of which is gene-specific. This behavior of H1, H2, H3, H4, and AMBP mRNAs in rat liver is in keeping with more limited analyses m ade at mRNA and/or protein levels in other species (human, pig) suffer ing from an acute inflammation. Therefore, the inflammation-associated regulation of these live genes that is conserved between species indi cates that the inter-alpha-inhibitor family members are likely to be i mportant partners of the acute phase response. (C) 1998 Academic Press .