Interferon‐gamma, tumor necrosis factor‐alpha, and lipopolysaccharide promote chitotriosidase gene expression in human macrophages

Abstract

Human chitotriosidase (Chit), a chitinolytic enzyme, is a member of the chitinase family. In human plasma, Chit activity has been proposed as a biochemical marker of macrophage activation in several lysosomal diseases. Recently we found that Chit activity is higher in patients affected by Plasmodium falciparum malaria infection, suggesting that Chit may reflect induction of an immunological response. To assess this hypothesis, we evaluated the CHIT1 mRNA levels in human monocytes/macrophages (HMMs) following treatment with interferon-gamma (IFNgamma), tumor necrosis factor-alpha (TNFalpha), and lipopolysaccharide (LPS). Stimulation of macrophages with INF-gamma, TNF-alpha, and LPS resulted in an increase in Chit activity as well as the levels of CHIT1 mRNA as measured by quantitative real-time PCR. The data presented in this article show that Chit plays a role in the response to the activation of INF-gamma-, TNF-alpha-, and LPS-driven macrophages, suggesting that the production of Chit by macrophages could have biological relevance in the immune-response.

Lung Chitinolytic Activity and Chitotriosidase Are Elevated in Chronic Obstructive Pulmonary Disease and Contribute to Lung Inflammation

“…3,27,28 We found that amounts of IL-1␤, TNF-␣ and of its type II soluble receptor, TNF-RII, were elevated in BAL from patients with COPD, as compared to smokers without COPD, or to never-smokers. Chitinolytic activity and levels of ChTRase significantly correlated with the concentrations of IL-1␤, TNF-␣, and TNF-RII in BAL supporting the hypothesis of a mutual regulation in the production of these mediators in the airways of patients with COPD.…”

Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians

“…[26][27] Recently, it has been shown that CHIT-1 may be involved in the progression of nonalcoholic steatohepatitis. [28][29] Overall, these data underline the idea that CHIT-1, as an important factor in inflammation, 15 could have widespread effects on aging phenotypes, particularly on cardiovascular disease and dementia, and as such may influence the ability to achieve a long and healthy life. In a study conducted on healthy elderly subjects (aged 65-94 years), it has been reported that levels of serum CHIT was higher compared with that in young people.…”

“…This study indicates that the heterozygosity of the 24-bp duplication in the CHIT-1 gene could have a protective effect in human longevity. It is noteworthy that CHIT-1, as an important factor in inflammation, 15 could have widespread effects on aging phenotypes, particularly on cardiovascular disease [23][24] and dementia, [26][27] and as such may influence the ability to achieve a long and healthy life. In fact, the baseline examination suggested that oldest old subjects were markedly healthier than controls, despite the fact that these subjects were, on an average, 30-37 years older.…”

“…[11][12] CHIT-1 mRNA expression is upregulated after stimulation by tumor necrosis factor alpha (TNF-a), interferon gamma (IFN-g), prolactin and lipopolysaccharide (LPS). [13][14][15] In vitro studies using recombinant human CHIT-1 have demonstrated that CHIT-1 lyses the hyphal tip of Mucor rouxii and inhibits the growth of hyphae of Candida albicans. 6 In vivo, neutropenic mice challenged with lethal doses of C. albicans or with Aspergillosis exhibit increased survival when treated with human recombinant CHIT-1.…”

Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

“…Increased ChT activity was also recorded in several other diseases, such as Niemann-Pick (Brinkman et al 2005), GM1 gangliosidosis , b-thalassemia (Barone et al 1999), sarcoidosis (Boot et al 2010), malaria (Barone et al 2003), atherosclerosis (Artieda et al 2003;Boot et al 1999), and fungal and bacterial infections (Iyer et al 2009;Labadaridis et al 1998). The role of ChT enzyme is unclear, but a possible role in defense against chitin-containing pathogens and host immune response has been suggested (Choi et al 2001;Di Luca et al 2007;Di Rosa et al 2005;Gordon-Thomson et al 2009;Malaguarnera et al 2005;van Eijk et al 2005).…”