As mentioned above, myeloperoxidase also selleck screening library fulfilled our criteria for candidate selection. Although a suitable ELISA assay is available, the verification and validation of exploratory proteomic findings will be covered elsewhere. Thus, this work focused solely on the potential of cathelicidin to discriminate the group of PPROM women with MIAC leading to HCA from the women in whom both conditions were ruled out. Several lines of evidence support a likely association of cathelicidin with MIAC leading to HCA. Cathelicidin is produced and released from epithelial cells, macrophages, and most importantly neutrophils upon stimulation by microorganisms. It was proved to be secreted in high amounts in tissues exposed to environmental microbes, particularly in those with squamous epithelia (mouth, tongue, cervix, vagina, esophagus, etc.

) or in derived fluids [26]. It is expressed in a form of an inactive preprotein, which has to be proteolytically cleaved into antibacterial LL-37 peptide [27]. The crucial role of cathelicidin in fighting infection has been demonstrated both in patients [28], [29] and in experimental animal models, where cathelicidin-deficient mice were found to be more prone to infection [30], [31]. The antimicrobial effect was also confirmed experimentally in body fluids, including amniotic fluid or urine [30], [32]. Similar findings lead to elucidation of the supposed antimicrobial effect of vitamin D, which can activate cathelicidin production along with bacteria and viruses [33], [34].

The proposed mechanism of action is triggered by Toll-like receptor 2/1 activation, which leads to the production of 25-hydroxyvitamin D-1 ��-hydroxylase, which in turn converts inactive 25-hydroxyvitamin D into active 1,25-dihydroxyvitamin D. This active form eventually binds to vitamin D receptor, a transcription factor that activates cathelicidin gene transcription [35]. The association between cathelicidin and vitamin D may be also regarded from another point of view. While vitamin D promotes antimicrobial agent production, it also has anti-inflammatory effects [36]. Even the ��executing�� Carfilzomib component of the antimicrobial effect, cathelicidin, was shown to have anti-inflammatory influence [37]. Several studies have shown, that maternal vitamin D deficiency is associated with a range of pregnancy related morbidities and adverse neonatal outcome [38]�C[42]. It can be speculated, that low levels of vitamin D may result in impaired production of antimicrobial peptides, which in turn could lead to reduced ability of facing microbial invasion. Given the fact that infection and/or inflammation are regarded as key components of causes leading to preterm birth, low vitamin D levels might be associated with increased risk of preterm labour [43].