Modulation of chitinases and chitinase like proteins duringmacrophage differentiation and polarization

Author(s): Michelino Di Rosa, Francesca Lazzara, Gisella Di Stefano, Daniela Cambria,AnnaMaria Longo, Lucia Malaguarnera

Enzymatically active chitinases chitotriosidase (CHIT-1) and AMC-ase as well as Chitinase Like Proteins YKL-40, YKL-39 have specific patterns of association with immune response. Serum levels of CHIT-1 and YKL-40 mainly reflect the activation status of macrophages, and in particular lipid-laden macrophages.While chitotriosidase is a specific marker for lysosomal storage disorders, overexpression of YKL-40 was found in numerous of tumors, chronic and acute inflammations and during fibrosis progression. We compared the Chitinases variations during the differentiation and polarization of humanmacrophages.Gene expression analysis was investigated by real-time PCR from mRNA of human monocytes obtained from buffy coat of healthy volunteers, polarized to classically activated macrophages (or M1), whose prototypical activating stimuli are Interferon-gamma and lipopolysaccharide, and alternatively activated macrophages (or M2) obtained by interleukin-4 exposure. We found that CHIT-1 and YKL-40 were significantly modulated throughout monocyteto- macrophage differentiation and polarization. In contrast, AMC-ase, YKL-39 showed slight modulation in the diverse stage of macrophages differentiation and/or polarization. In conclusion our results show that the expression of CHIT-1 AMC-ase, YKL-40 and YKL-39 is differentially regulated throughout monocyte-to-macrophage differentiation and polarization. Our finding suggests that whereas the immune function of AMC-ase and YKL-39 is restricted and selective, CHIT-1 and YKL-40 are protagonists in innate and acquired immunity.

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