Fibroblast Response to Lanthanoid Metal Ion Stimulation: Potential Contribution to Fibrotic Tissue Injury

• Published in: Biological trace element research 2011-12, Vol.144 (1-3), p.621-635
• Main Authors: Jenkins, William, Perone, Patricia, Walker, Kyle, Bhagavathula, Narasimharao, Aslam, Muhammad Nadeem, DaSilva, Marissa, Dame, Michael K, Varani, James
• Format: Article
• Language: English
• Subjects: Aluminum; Apoptosis - drug effects; Bioassays; Biochemistry; Biomedical and Life Sciences; Biotechnology; Blotting, Western; Cadherins - biosynthesis; Cadherins - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Cobalt; Collagen Type I - biosynthesis; copper; culture media; Enzymes; fibroblasts; Fibroblasts - drug effects; Fibrosis - chemically induced; Fibrosis - pathology; Humans; Indicators and Reagents; interstitial collagenase; Ions; iron; keratinocytes; Keratinocytes - drug effects; Lanthanoid Series Elements - pharmacology; Life Sciences; Magnesium; Manganese; Matrix Metalloproteinase 1 - biosynthesis; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 2 - genetics; Metal concentrations; Metal ions; Metals; Nickel; Nutrition; Oncology; Proteins; Skin - cytology; Skin - pathology; Stimulation, Chemical; Tissue Inhibitor of Metalloproteinase-1 - biosynthesis; Transition Elements - pharmacology; zinc
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-011-9041-x

The purpose of this study was to compare each of the 14 naturally occurring lanthanoid metal ions for ability to stimulate pro-fibrotic responses in human dermal fibroblasts. When fibroblasts were exposed to individual lanthanoids over the concentration range of 1–100 μM, increased proliferation was observed with each of the agents as compared with control cells that were already proliferating rapidly in a growth factor-enriched culture medium. Dose–response differences were observed among the individual metal ions. Matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 levels were also increased in response to lanthanoid exposure but type I procollagen production was not. A dose–response relationship between induction of proliferation and increased MMP-1 was observed. Non-lanthanoid transition metal ions (aluminum, copper, cobalt, iron, magnesium, manganese, nickel, and zinc) were examined in the same assays; there was little stimulation with any of these metals. When epidermal keratinocytes were examined in place of dermal fibroblasts, there was no growth stimulation with any of the lanthanoids. Several of the lanthanoid metals inhibited keratinocyte proliferation at higher concentrations (50–100 μM).