Regulation of signal transducer, GP13O and the LIF receptor in acute inflammation in vivo.
Recently we examined the expression of the IL-6 receptor (gp80) in three different models of acute inflammation [Geisterfer et al., 1993, Cytokine 5:1]. To continue these studies, we examined the mRNA expression of signal transducing molecule, gp130, and the LIF-R as associated members of a receptor family. Rats were treated with either Freund's complete adjuvant (FA) via intraperitoneal injection, LPS via intravenous injection, or turpentine via subcutaneous injection. The levels of gp130 and LIF-R mRNA expression had a maximum 2-3-fold increase over a 24 h period. However, the time of the maximum increase differed depending on the treatment the rats received. FA treated rats had a maximum induction of gp130 mRNA levels of 2.2-fold (for the 7.5 kb transcript) and 1.3-fold (for the 9.0 kb transcript) at 12 h. LPS treated rats had a maximum increase at 3 h where message levels increased 2.5-fold (7.5 kb) and 1.2-fold (9.0 kb). Turpentine-injected rats showed little difference in gp130 mRNA levels at any time after injection compared to controls. Maximum LIF-R mRNA levels also differed depending on the type of treatment the rats received. FA-injected rats showed a 2.1-fold mRNA increase at 3 h, whereas LPS treated rats show a maximum 2.4-fold increase at 18 h. Turpentine-injected rats showed little increase in mRNA levels compared to controls. Injection of purified recombinant rat IL-6 (rIL-6) had little effect on LIF-R mRNA levels, but had a dramatic inducing effect on gp130 mRNA levels. Rats were also injected (i.p.) with Dexamethasone (Dex) and this had no effect on either gp130 or LIF-R mRNA level expression. These in vivo results indicated that IL-6 has a major role in the regulation of its own receptors, IL-6R (gp80), and gp130, and the onset of acute phase response. We found that the maximum IL-6R (gp80), gp130 and LIF-R mRNA levels peaked at different times depending on the type of acute inflammation induced in the rat. It seems that various combinations of cytokines and hormones are released depending on the type of acute inflammation, and these in turn regulate the expression of diverse receptors on the hepatocyte, resulting in different acute phase kinetics in the various models of inflammation.
Geisterfer
M
M
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Gauldie
J
J
D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D050822:Cytokine Receptor gp130; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D006131:Growth Inhibitors; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008222:Lymphokines; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*; D053606:Receptors, OSM-LIF; D015398:Signal Transduction / Q000502:physiology*; D014425:Turpentine
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D006131:Growth Inhibitors; C494201:Il6st protein, rat; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507842:Lifr protein, rat; D008070:Lipopolysaccharides; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D050822:Cytokine Receptor gp130; D003907:Dexamethasone; D005620:Freund's Adjuvant; D014425:Turpentine