title: Aluminum induces inflammatory and proteolytic alterations in human monocytic cell line.
abstract: The increasing exposure to aluminum has been linked with the development of different human pathologies (e.g., breast cancer, myofasciitis, neurodegenerative diseases), probably due to the consistent presence of aluminum salts in widely diffused cosmetic products and vaccines. However, the mechanisms underlying immunologic and proliferative alterations still remain unknown. In the present study we investigated the ability of different aluminum compounds (i.e., aluminum chloride vs Imject® Alum, a mixture of aluminum and magnesium hydroxide) to trigger both inflammatory and proteolytic responses in U-937 human monocytic cell line. We demonstrated, by multiplex immunoassay analyses, that monocytic cells treated with both Imject Alum and aluminum chloride showed different and peculiar expression profiles of 27 inflammatory mediators and 5 matrix metalloproteinases, with respect to untreated control cells. In particular, we found dose-dependent significantly increased levels of pro-inflammatory cytokines, growth factors, and chemoattractant chemokines; whereas among metalloproteinases, only collagenolytic protease showed a significant dose-dependent increase in Imject-treated cells with respect to controls and Al-chloride treated cells. Noteworthy, we found only in Imject Alum-treated cells the significant positive correlations among collagenolytic metalloproteinase and increased expression of pro-inflammatory chemokines, suggesting a possible involvement of aluminum in regulating the acute inflammatory responses. In agreement to emerging evidences, for the first time we demonstrated that the treatment of monocyte cells with aluminum-based adjuvant is able to induce an inflammatory status and a proteolytic cascade activation. In fact, the cell treatment with Imject Alum induced increased levels of several cytokines and proteinases, suggesting these monocyte mediators as possible biomarkers for aluminum-linked diseases. The identification of the biochemical pathways involved in Al-induced cell injury pave the way for improving the knowledge on the potential impact of aluminum in human physio-pathology.
authors.affiliation: Department of Biomolecular Sciences, Section of Clinical Biochemistry and Cell Biology, University "Carlo Bo", Urbino, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Ligi
authors.affiliation: Department of Biomolecular Sciences, Section of Clinical Biochemistry and Cell Biology, University "Carlo Bo", Urbino, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Santi
authors.affiliation: Department of Biomolecular Sciences, Section of Clinical Biochemistry and Cell Biology, University "Carlo Bo", Urbino, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Croce
authors.affiliation: Department of Biomolecular Sciences, Section of Clinical Biochemistry and Cell Biology, University "Carlo Bo", Urbino, Italy. Electronic address: ferdinando.mannello@uniurb.it.
authors.forename: F
authors.initials: F
authors.lastname: Mannello
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000535:Aluminum / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects*
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D000535:Aluminum; D020782:Matrix Metalloproteinases
keywords: Aluminum chloride; Chemokines; Cytokines; Imject Alum; Matrix metalloproteinases; Multiplex immunoassay