Dissecting neutrophilic inflammation in cystic fibrosis lung disease: the role of chitinases

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Chitin, the second most abundant polysaccharide in nature after cellulose, is an essential component of exoskeletons of fungi, parasites and insects. Chitin is degraded by chitinases, produced by lower life forms to defend against infections with chitin-containing organisms. It has been assumed that mammals lack chitinases, but recent studies showed that humans express both chitinases and chitinase-like proteins. Recent studies from our lab provide evidence that (i) chitinase-like proteins accumulate in the airways of cystic fibrosis (CF) patients, (ii) Chitinase-like proteins are upregulated in lungs from a CF mouse model, (iii) chitinase-like proteins correlate with pulmonary obstruction in CF lung disease, (iv) chitinase-like proteins are regulated genetically and (v) CF cells release enhanced active chitinases. Based on these observations, we hypothesize that chitinase-like proteins and chitinases modulates CF lung disease. However, the underlying mechanisms are poorly understood. Therefore, we aim to perform the following studies: (i) To investigate the role of CFTR in regulating the release of chitinases and chitinase-like proteins, (ii) to dissect the functionalities of chitinases and chitinase-like proteins in the context of CF and to (iii) therapeutically target chitinases and chitinase-like proteins in murine models of CF lung disease in vivo. These studies could pave the way for the development of specific drugs targeting chitinases and chitinase-like proteins, which could become a novel treatment strategy in CF and other chronic inflammatory diseases.