Expression of sarcoidosis related genes in lung lavage cells.
BACKGROUND
Sarcoidosis is a systemic granulomatous multiorgan disease of unknown cause. Some facts point to a genetically determined predisposition, like associations with certain Major Histocompatibility Antigens Class I- and II-types (MHC). Mycobacterial DNA has been found in about 30% of sarcoidosis patients within the granulomas, which has been interpreted as a probable trigger mechanism.


METHODS
Cells from bronchoalveolar lavage (BAL) of sarcoidosis patients were stimulated with dead Mycobacterium avium and gene expression was studied after six hours. Gene expression was profiled by hybridization to PCR filters (Human UniGene Set RZPD-1). To avoid the detection of effects related to secondary and tertiary inflammatory messages, we compared gene expression in sarcoidosis with that of tuberculosis and extrinsic allergic alveolitis. After normalization genes up- or downregulated for a factor of at least 1.8 were further analyzed. Genes differentially expressed in sarcoidosis as well as in tuberculosis or EAA, respectively, were subtracted.


CONCLUSIONS
Four different genes were exclusively upregulated in sarcoidosis: fatty acid binding protein 4 (FABP4), B-MYB, and two EST's. FABP4 has already been described in some autoimmune diseases, but its function in sarcoidosis is unknown. B-MYB is a potent growth factor for haematopoietic cells including lymphocytes. It might be one of the central genes upregulated in sarcoidosis and by that inducing clonal expansion of sarcoidosis-antigen primed T-helper-lymphocytes. Clonal selection of T-helper cells might be facilitated by c-Akt together with Tcl-1, both also upregulated in sarcoidosis. For the two ESTs neither function nor location is known.
Thonhofer
Rene
R
Laboratories for Molecular Cytogenetics, Environmental and Respiratory Pathology, Institute of Pathology, Karl Franzens University of Graz, Austria.
Maercker
Christian
C
Popper
Helmut H
HH
D000542:Alveolitis, Extrinsic Allergic / Q000235:genetics; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002352:Carrier Proteins / Q000235:genetics; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000235:genetics; D015870:Gene Expression; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008168:Lung / Q000648:ultrastructure*; D009162:Mycobacterium avium / Q000235:genetics; D009363:Neoplasm Proteins; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt; D012507:Sarcoidosis / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000235:genetics; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D002352:Carrier Proteins; C493410:FABP4 protein, human; C107608:FABP7 protein, human; C493411:Fabp4 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; C490393:Tcl1 protein, mouse; D025521:Tumor Suppressor Proteins; D011505:Protein-Tyrosine Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt