PMID- 9341739
OWN - NLM
STAT- MEDLINE
DCOM- 19971113
LR  - 20041117
IS  - 0008-8749 (Print)
IS  - 0008-8749 (Linking)
VI  - 180
IP  - 2
DP  - 1997 Sep 15
TI  - Inhibition of IL-10 protein synthesis induces major histocompatibility complex 
      class II gene expression in class II-deficient patients.
PG  - 95-103
AB  - Major histocompatibility complex (MHC) class II deficiency is an inherited 
      autosomal recessive combined immunodeficiency, characterized by a lack of 
      constitutive expression of the human leukocyte antigen (HLA) class II genes. The 
      patients investigated in this study are histoidentical twin brothers with a new 
      phenotype in MHC class II deficiency. Examination of HLA-D locus genes in their 
      fractionated peripheral mononuclear cells (MNCs) revealed an unusual and 
      uncoordinated mRNA pattern. Here we analyzed the distribution of pro- and 
      anti-inflammatory cytokines expressed in these patients' adherent and nonadherent 
      MNCs. We show that gene expression of IL-1 alpha, IL-1 beta, IL-6, 
      granulocyte-colony-stimulating factor, and IL-10 was induced in both cell 
      fractions, whereas increased mRNA levels of interferon-gamma and the inducible 
      nitric oxide synthase were exclusively detected in the patients' nonadherent 
      MNCs. As IL-10 is known to be able to downregulate transcription of MHC class II 
      and expression of IL-10 in the patients' MNCs was increased, we investigated the 
      regulatory function of this cytokine. Interestingly, inhibition of IL-10 protein 
      synthesis with IL-10-specific antisense oligonucleotide DNA (IL-10-AS-ODN) 
      induced HLA-D locus genes in these MHC class II-deficient patients. Exposure of 
      the nonadherent cell fraction to IL-10-AS-ODN resulted in a profound induction of 
      a previously absent DR beta 1 and DP alpha gene expression. HLA-DQ beta mRNA 
      levels, however, were increased in both the adherent and the nonadherent MNC 
      population. Albeit expression of HLA-D locus genes was inducible via inhibition 
      of IL-10 translation, surface expression of HLA class II antigens on the 
      patients' MNCs was essentially negative. The data presented support the concept 
      of a coordinated network of pro- and anti-inflammatory cytokine regulation and 
      this network obviously has a significant role in the cell-type-specific 
      regulation of MHC class II expression.
FAU - Hauber, I
AU  - Hauber I
AD  - Institute of Clinical and Molecular Virology, University Erlangen Nurnberg, 
      Germany. iahauber@viro.med
FAU - Wolf, H M
AU  - Wolf HM
FAU - Samstag, A
AU  - Samstag A
FAU - Pein, B
AU  - Pein B
FAU - Kreil, T R
AU  - Kreil TR
FAU - Gulle, H
AU  - Gulle H
FAU - Fischer, M B
AU  - Fischer MB
FAU - Eibl, M M
AU  - Eibl MM
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (Cytokines)
RN  - 0 (HLA-D Antigens)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (RNA, Messenger)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Cells, Cultured
MH  - Cytokines/physiology
MH  - *Gene Expression Regulation
MH  - *Genes, MHC Class II
MH  - HLA-D Antigens/*metabolism
MH  - Humans
MH  - Interleukin-10/*biosynthesis
MH  - Leukocytes, Mononuclear/physiology
MH  - Male
MH  - Oligonucleotides, Antisense/pharmacology
MH  - RNA, Messenger/genetics
EDAT- 1997/10/28 00:00
MHDA- 1997/10/28 00:01
CRDT- 1997/10/28 00:00
PHST- 1997/10/28 00:00 [pubmed]
PHST- 1997/10/28 00:01 [medline]
PHST- 1997/10/28 00:00 [entrez]
AID - S0008-8749(97)91170-9 [pii]
AID - 10.1006/cimm.1997.1170 [doi]
PST - ppublish
SO  - Cell Immunol. 1997 Sep 15;180(2):95-103. doi: 10.1006/cimm.1997.1170.