title: Lithium chloride promotes host resistance against Pseudomonas aeruginosa keratitis.
abstract: OBJECTIVE
  To explore the role of lithium chloride (LiCl) in Pseudomonas aeruginosa (PA) keratitis.
  
  
  METHODS
  B6 mice were subconjunctivally injected with LiCl in contrast to appropriate control sodium chloride (NaCl), and then routinely infected with PA. Clinical score, slit-lamp photography, hematoxylin and eosin (H&E) staining, and bacterial plate counts were used to determine the role of LiCl in PA keratitis. Messenger ribonucleic acid and protein levels of inflammatory cytokines in PA-challenged mouse corneas and in vitro cultured macrophages and neutrophils were measured with real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Apoptosis of the infiltrating inflammatory cells in the PA-infected murine corneas was assessed using terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and propidium iodide staining associated with flow cytometry. In cultured murine macrophages and neutrophils, cell apoptosis was determined with annexin V/propidium iodide double staining associated with flow cytometry and western blot analysis for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase.
  
  
  RESULTS
  Treatment with LiCl reduced the severity of corneal disease by reducing corneal inflammatory response and bacterial burden. Moreover, LiCl increased anti-inflammatory cytokine interleukin-10 levels, decreased proinflammatory cytokine tumor necrosis factor-α levels, and enhanced apoptosis of infiltrating macrophages and neutrophils in the PA-infected mouse corneas. In vitro studies further confirmed that LiCl elevated anti-inflammatory cytokine expression but reduced proinflammatory cytokine production, as well as promoted cell apoptosis in murine macrophages and neutrophils.
  
  
  CONCLUSIONS
  This study demonstrates a protective role of LiCl in PA keratitis. LiCl promotes host resistance against PA infection by suppressing inflammatory responses, enhancing inflammatory cell apoptosis, and promoting bacterial clearance.
authors.affiliation: Department of Immunology, Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Qiuchan
authors.initials: Q
authors.lastname: Deng
authors.forename: Xinxin
authors.initials: X
authors.lastname: Nie
authors.forename: Meiyu
authors.initials: M
authors.lastname: Li
authors.forename: Minhao
authors.initials: M
authors.lastname: Wu
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D060467:Disease Resistance / Q000187:drug effects* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000187:drug effects* / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D007634:Keratitis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*; D018021:Lithium Chloride / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D020011:Protective Agents; D018021:Lithium Chloride