ABSTRACT
The multiple enzymatic activities and functions of transglutaminase type 2 (TG2) may be attributed to alternative TG2 molecules produced by differential splicing of TG2 mRNA. Different RNA transcripts of the human TG2 gene (TGM2) have been identified, but the expression of TG2 multiple transcripts has never been systematically addressed. We have confirmed and rationalized the main TG2 variants and developed a screening assay for the detection of alternative splicing of TG2, based on real-time reverse-transcription PCR. We have quantified the multiple TG2 transcripts in a wide range of normal tissues and in cancer cell lines from four different sites of origin. Our data show a significant correlation in the expression of canonical and alternative TG2 isoforms in normal human tissue, but differences in alternative splicing of TG2 in cancer cell lines, suggesting that in cancer cells the alternative splicing of TG2 is a more active process.
Subject(s)
Adenocarcinoma/enzymology , Alternative Splicing , Gene Expression , Prostatic Neoplasms/enzymology , Transglutaminases/metabolism , Adenocarcinoma/genetics , Aged , Amino Acid Sequence , Base Sequence , Cell Line, Tumor , GTP-Binding Proteins , Humans , Isoenzymes/genetics , Isoenzymes/metabolism , Male , Molecular Sequence Data , Prostatic Neoplasms/genetics , Protein Glutamine gamma Glutamyltransferase 2 , RNA Splice Sites , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Transglutaminases/geneticsABSTRACT
The C-reactive protein (CRP), an acute phase reactant which binds selectively to T (thymus-derived) lymphocytes, was found to bind to lymphoblasts formed upon stimulation with antigens but not with mitogens. Binding of CRP thus serves as a marker for antigen-reactive (-reacted) as opposed to mitogen-reative (-reacted) T cells, suggesting that these represent separate subpopulations, and supports the developing concept that CRP play an important role in the regulation of responses critical to inflammation, host defense, and tissue repair.
Subject(s)
C-Reactive Protein/metabolism , Histocompatibility Antigens , Mitogens , T-Lymphocytes/immunology , Tuberculin , Antigens , Cell Differentiation , Humans , Lymphocytes/metabolism , Protein Binding , T-Lymphocytes/cytology , T-Lymphocytes/metabolismABSTRACT
Several in vitro studies have demonstrated a polyclonal B cell response to antigenic stimulation in patients with systemic lupus erythematosus (SLE). To determine if this polyclonal response occurs in vivo, 18 patients with SLE were antigenically stimulated with the pneumococcal vaccine Pneumovax . Mean antibody response to immunization was the same in SLE and normal control subjects. Although elevated antibody levels to several viruses were present in SLE subjects preimmunization, these levels did not change postimmunization. Total immunoglobulin levels, immune complex levels, and antiblood group B antibody levels did not change in SLE patients after immunization. Antiblood group A titers rose in both SLE patients and normals due to a media contaminant in the Pneumovax . Thus, SLE patients appear to have a specific antibody response to antigenic stimulation with pneumococcal polysaccharide. Polyclonal activation as seen in vitro in SLE may be more restricted in vivo.