TY - JOUR
T1 - Two regions of the H-2 Dd promoter are responsive to dimethylsulfoxide in line 1 cells by a mechanism distinct from ifn-γ
AU - Cerosaletti, K. M.
AU - Woodward, J. G.
AU - Lord, E. M.
AU - Frelinger, J. G.
PY - 1992/2/15
Y1 - 1992/2/15
N2 - The line 1 lung carcinoma is a spontaneous BALB/ c tumor deficient in class I Ag expression at the protein and mRNA levels. Exposure of line 1 cells to 3% DMSO or IFN-γ increases class I Ag protein and mRNA dramatically. We have examined the regulation of class I Ag induction by DMSO in line 1 cells. We found DMSO induces class I Ag expression in line 1 cells by a mechanism distinct from IFN, because the kinetics of class I Ag induction by these agents were dramatically different, 7 days vs 3 days, and DMSO did not act through an IFN second messenger. At the molecular level, class I H chain transcription in line 1 cells was low. Treatment with 3% DMSO or IFN-γ increased H chain transcription fourfold and sevenfold, respectively, indicating that class I H chain expression is regulated at the level of transcription in line 1 cells. Using reporter gene constructs, we mapped the regions in the Dd H chain promoter that increase H chain expression after DMSO treatment of line 1 cells. Two regions of the Dd promoter, D1, from -210 to -133 bp, and D2, from -125 to -61 bp, were found to be independently responsive to DMSO. These regions were also responsive to IFN-γ in line 1 cells. However, consistent with our cellular results, DMSO and IFN induction of class I H chain expression differed at the molecular level as determined by D1 point mutations that diminished IFN-γ responsiveness but did not alter induction by DMSO. Thus, DMSO appears to regulate class I transcription through multiple regions of the class I H chain promoter in line 1 cells by a mechanism distinct from IFN-γ.
AB - The line 1 lung carcinoma is a spontaneous BALB/ c tumor deficient in class I Ag expression at the protein and mRNA levels. Exposure of line 1 cells to 3% DMSO or IFN-γ increases class I Ag protein and mRNA dramatically. We have examined the regulation of class I Ag induction by DMSO in line 1 cells. We found DMSO induces class I Ag expression in line 1 cells by a mechanism distinct from IFN, because the kinetics of class I Ag induction by these agents were dramatically different, 7 days vs 3 days, and DMSO did not act through an IFN second messenger. At the molecular level, class I H chain transcription in line 1 cells was low. Treatment with 3% DMSO or IFN-γ increased H chain transcription fourfold and sevenfold, respectively, indicating that class I H chain expression is regulated at the level of transcription in line 1 cells. Using reporter gene constructs, we mapped the regions in the Dd H chain promoter that increase H chain expression after DMSO treatment of line 1 cells. Two regions of the Dd promoter, D1, from -210 to -133 bp, and D2, from -125 to -61 bp, were found to be independently responsive to DMSO. These regions were also responsive to IFN-γ in line 1 cells. However, consistent with our cellular results, DMSO and IFN induction of class I H chain expression differed at the molecular level as determined by D1 point mutations that diminished IFN-γ responsiveness but did not alter induction by DMSO. Thus, DMSO appears to regulate class I transcription through multiple regions of the class I H chain promoter in line 1 cells by a mechanism distinct from IFN-γ.
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M3 - Article
C2 - 1737936
AN - SCOPUS:0026558590
SN - 0022-1767
VL - 148
SP - 1212
EP - 1221
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -