title: Zoledronic acid affects the cytotoxic effects of Chlamydia pneumoniae and the modulation of cytokine production in human osteosarcoma cells.
abstract: Chlamydia pneumoniae is an obligate intracellular Gram-negative bacterium that causes persistent infections with a tendency to chronicize, which might motivate the resistance of chlamydiae to some commonly used antibiotics. The bisphosphonates are an emerging class of drugs mostly used in the palliative care of cancer patients to inhibit proliferation and metastasis of cancer cells but their role in modulating immune responses remains unknown. We investigated the in vitro activity of a highly potent bisphosphonate, zoledronic acid, on the cytotoxic effects of C. pneumoniae in human SaOS-2 osteoblast-like cells and the consequent immune response carried out by this cell line. We have reported that zoledronic acid showed a significant anti-proliferative effect on SaOS-2 cell line infected by C. pneumoniae in a time- and dose-dependent manner. We have also found that zoledronic acid induced growth inhibition of C. pneumoniae. Our data showed that C. pneumoniae-infection of SaOS-2 cells induced a significant gene expression of proinflammatory cytokines TNF-α, IL-6, IL-8 and IL-12, detected by RT-PCR, and confirmed by protein release assay. Our results demonstrated that zoledronic acid could facilitate C. pneumoniae-mediated immune response, thus reprofiling this traditional anti-tumor drug as a novel immune regulator in promoting host defense against C. pneumoniae infection.
authors: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Faculty of Medicine and Surgery, Second University of Naples, Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy. Electronic address: antonietta.rizzo@unina2.it.
authors: Antonietta
authors: A
authors: Rizzo
authors: Department of Biochemistry, Biophysics and General Pathology, Faculty of Medicine and Surgery, Second University of Naples, Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy.
authors: Gabriella
authors: G
authors: Misso
authors: Department of Clinical Pathology, A. Cardarelli Hospital, Via Antonio Cardarelli, 9, 80133 Naples, Italy.
authors: Nazario
authors: N
authors: Bevilacqua
authors: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Faculty of Medicine and Surgery, Second University of Naples, Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy.
authors: Giovanna
authors: G
authors: Donnarumma
authors: Department of Biochemistry, Biophysics and General Pathology, Faculty of Medicine and Surgery, Second University of Naples, Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy.
authors: Angela
authors: A
authors: Lombardi
authors: Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Faculty of Medicine and Surgery, Second University of Naples, Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy.
authors: Massimiliano
authors: M
authors: Galdiero
authors: Department of Biochemistry, Biophysics and General Pathology, Faculty of Medicine and Surgery, Second University of Naples, Via Santa Maria di Costantinopoli, 16, 80138 Naples, Italy.
authors: Michele
authors: M
authors: Caraglia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D023521:Chlamydophila Infections / Q000188:drug therapy* / Q000276:immunology; D016993:Chlamydophila pneumoniae / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007113:Immunity, Innate / Q000187:drug effects; D056747:Immunomodulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D015854:Up-Regulation; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D004164:Diphosphonates; D007093:Imidazoles; D018836:Inflammation Mediators; D000077211:Zoledronic Acid
keywords: Bisphosphonates; Chlamydia pneumoniae; Cytokines; Cytotoxicity; Human osteosarcoma cells; Zoledronic acid