The reprogrammed host - Chlamydia trachomatis - Induced up-regulation of glycoprotein 130 cytokines, transcription factors, and antiapoptotic genes

Objective. Infection with Chlamydia trachomatis is a known cause of sexuall y transmitted diseases, eye infections (including trachoma), and reactive a rthritis (ReA). Because the mechanisms of Chlamydia-induced changes leading to ReA are poorly defined, this study sought to identify the target genes involved at the molecular level. Methods. Chlamydia-induced changes in host cells were investigated by combi ning a screening technique, which utilized complementary DNA arrays on C tr achomatis-infected and mock-infected epithelial HeLa cells, with real-time reverse transcription-polymerase chain reaction or enzyme-linked immunosorb ent assay of gene products. Some responses were additionally demonstrated o n human primary chondrocytes and a human synovial fibroblast cell line, bot h of which served as model cells for ReA. Results. Eighteen genes (of 1,176) were found to be up-regulated after 24 h ours of infection with this obligate intracellular bacterium, among them th e glycoprotein 130 family members IL-11 and LIF, the chemokine gene MIP2-al pha, the transcription factor genes EGR1, ETR101, FRA1, and e-jun, the apop tosis-related genes IEX-1L and MCL-1, adhesion molecule genes such as ICAM1 , and various other functionally important genes. In the context of this rh eumatic disease, the cytokines and transcription factors seem to be especia lly involved, since various connections to chondrocytes, synoviocytes, bone remodeling, joint pathology, and other rheumatic diseases have been demons trated. Conclusion. Infection with C trachomatis seems to reprogram the host cells (independent of activation by lipopolysaccharide or other ultraviolet-resis tant bacterial components) at various key positions that act as intra- or i ntercellular switches, suggesting that these changes and similar Chlamydia- induced functional alterations constitute an important basis of the pathoge nic inflammatory potential of these cells in ReA. Our results suggest that this approach is generally useful for the broad analysis of host-pathogen i nteractions involving obligate intracellular bacteria, and for the identifi cation of target genes for therapeutic intervention in this rheumatic disea se.