Browsing by Subject "monosyytti"

Making the treatment of these infections even harder is the fact, that Chlamydia pneumoniae can produce persistent forms of itself, which are immune to antibiotic treatment. When the bacteria sense a stress factor, for example the presence of a β-lactam antibiotic or interferon γ, they start producing these persistent forms called aberrant bodies. When the stress factor is removed, the bacteria can switch back to their replicating form and start infecting the tissues again. It is also known, that C. pneumoniae bacteria will trigger persistence when the bacteria migrate from lung epithelia into monocytes. Interestingly the onset of this mode of persistence does not require any other triggers besides the invasion of the monocyte. These persistence mechanisms enable latent, quiet, and recurring infections. This master’s thesis aimed to study the coculture of lung epithelial (HL cells) and monocytes (THP-1 cells), and by utilising the magnetic separation method presented by Kortesoja et al, to find a positive control compound in the prevention of Chlamydia pneumoniae internalisation into the THP-1 cells for said protocol. In these cocultures the inhibitory effect of different compound groups such as lignans present in Schisandra chinensis plant, MAPK-inhibitors, and β2,2-amino acid derivatives in C. pneumoniae migration from HL cells to THP-1 cells was assessed. Statistic relevance was observed in JNK inhibitor SP600125, MAPKAP-kinase-2 inhibitor SB203580, and ERK1/2 inhibitor FR180204 compounds. These compounds inhibited the internalisation of Chlamydia pneumoniae into THP-1 cells in the cell coculture by 61,05 ± 16,63 % (p = 0,0001), 54,06 ± 16,02 % (p = 0,0002), and 36,76 ± 10,33 % (p = 0,009) respectively. SP600125 and SB 203580 compounds also had an inhibitory effect on the internalisation of C. pneumoniae into the THP-1 cells in a cell monoculture (39,98 ± 18,92 %, p = 0,026 and 37,89 ± 19,47 %, p = 0,035 respectively), whereas FR180204 had no statistical significance, even though it inhibited the internalisation of C. pneumoniae into the THP-1 cells in cell monoculture by 27,53 ± 21,17 %. From the compounds used in the experiments, only MAPK inhibitors had an effect in inhibiting the C. pneumoniae internalisation into the THP-1 cells. The most potent compound in said inhibition was the JNK inhibitor SP600125. JNK pathway has been thought to take part in chlamydial infections but only little research has been done. The results of this master’s thesis’ experiments support the thought of JNK enzyme taking part in chlamydial infections but determining how exactly it affects the infection cycle of C. pneumoniae bacteria still needs further investigation.