Il-6 levels, area of burn and the acute-phase reactant protein response

Burns ◽  
1993 ◽  
Vol 19 (4) ◽  
pp. 365
2010 ◽  
Vol 24 (2) ◽  
pp. 391-401 ◽  
Author(s):  
Sutapa Ray ◽  
Chang Lee ◽  
Tieying Hou ◽  
Kishor K. Bhakat ◽  
Allan R. Brasier

Abstract The signal transducer and activator of transcription-3 (STAT3) is a latent IL-6 inducible transcription factor that mediates hepatic and vascular inflammation. In this study, we make the novel observation that STAT3 forms an inducible complex with the apurinic/apyrimidinic endonuclease 1 (APE1)/redox effector factor-1 (APE1/Ref-1), an essential multifunctional protein in DNA base excision repair, and studied the role of APE1/Ref-1 in STAT3 function. Using a transfection-coimmunoprecipitation assay, we observed that APE1 selectively binds the NH2-terminal acetylation domain of STAT3. Ectopic expression of APE1 potentiated inducible STAT3 reporter activity, whereas knockdown of APE1 resulted in reduced IL-6-inducible acute-phase reactant protein expression (C-reactive protein and serum amyloid P) and monocyte chemotactic protein-1 expression. The mechanism for APE1 requirement in IL-6 signaling was indicated by reduced STAT3 DNA binding activity observed in response to small interfering RNA-mediated APE1 silencing. Consistent with these in vitro studies, we also observed that lipopolysaccharide-induced activation of acute-phase reactant protein expression is significantly abrogated in APE1 heterozygous mice compared with wild-type mice. IL-6 induces both STAT3 and APE1 to bind the suppressor of cytokine signaling-3 and γ-fibrionogen promoters in their native chromatin environment. Moreover, we observed that APE1 knockdown destabilized formation of the STAT3-inducible enhanceosome on the endogenous γ-fibrionogen promoter. Taken together, our study indicates that IL-6 induces a novel STAT3-APE1 complex, whose interaction is required for stable chromatin association in the IL-6-induced hepatic acute phase response.


1989 ◽  
Vol 170 (1) ◽  
pp. 349-354 ◽  
Author(s):  
D Bernuau ◽  
L Legrès ◽  
Y Lamri ◽  
N Giuily ◽  
G Fey ◽  
...  

Functional heterogeneity in the lobule with regard to plasma protein synthesis is still debated. Therefore, we have localized in liver sections from normal rats and from rats with turpentine-induced AIR the mRNA and protein products of three genes with different alterations in their hepatic expression during an AIR: alpha 2M and alpha 1PI, two positively reacting acute-phase genes, and alpha 1I3, a negative acute-phase reactant. In normal liver, all hepatocytes expressed alpha 2M and alpha 1I3 mRNA, but a preferential expression of alpha 2M and alpha 1I3 mRNA and protein in the PP and ML zones was observed. During an AIR, the level of alpha 2M mRNA increased fourfold in the cytoplasm of PP and ML hepatocytes, while the level of cytoplasmic alpha 1I3 mRNA was decreased about fourfold in the same zones, with parallel variations in the expression of the corresponding proteins. In contrast, no significant modulation of the RNA and protein concentrations of both genes was detected in PV areas. alpha 1PI mRNA was expressed at the same levels in the three lobular zones in normal liver, but staining for the alpha 1PI protein was more intense in the PV zones. During the acute-phase response alpha 1PI mRNA levels were increased twofold in all three lobular zones, and alpha 1PI staining became homogeneous within the lobule. These results demonstrate that the location of a hepatocyte with the liver lobule can influence the expression of the three genes under study both at pre- and post-translational levels, in basal conditions, as well as during modulation of their expression during the inflammatory reaction.


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