title: Latanoprost-induced Cytokine and Chemokine Release From Human Tenon's Capsule Fibroblasts: Role of MAPK and NF-κB Signaling Pathways.
abstract: OBJECTIVE
  Long-term topical antiglaucoma therapy is considered a significant risk factor for failure of trabeculectomy. We investigated the effects of antiglaucoma drugs on proinflammatory cytokine and chemokine release from cultured human Tenon's capsule fibroblasts (HTFs) as well as the signaling pathways that underlie such effects.
  
  
  METHODS
  Release of the proinflammatory cytokine interleukin (IL)-6 and the chemokines IL-8 and monocyte chemotactic protein (MCP)-1 was measured with enzyme-linked immunosorbent assays. The phosphorylation (activation) of mitogen-activated protein kinases (MAPKs) as well as the phosphorylation and degradation of the nuclear factor-κB (NF-κB) inhibitor IκB-α were assessed by immunoblot analysis.
  
  
  RESULTS
  Latanoprost stimulated the release of IL-6, IL-8, and MCP-1 from HTFs in a concentration-dependent and time-dependent manner, whereas timolol maleate and pilocarpine had no such effects. Latanoprost also activated the MAPKs extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase as well as induced the phosphorylation and degradation of IκB-α in these cells. The latanoprost-induced release of IL-6, IL-8, and MCP-1 was attenuated by inhibitors of MAPK (PD98059, SB203580, or JNK inhibitor II) or NF-κB (IκB kinase 2 inhibitor) signaling pathways.
  
  
  CONCLUSIONS
  Latanoprost induced proinflammatory cytokine and chemokine release from HTFs in a manner dependent on MAPK and NF-κB signaling. These effects of latanoprost might influence bleb scarring after filtration surgery.
authors.affiliation: Departments of *Pathology †Ophthalmology, First Hospital of Jilin University, Jilin ‡Institute of Environmental Systems Biology, Environmental Science and Engineering College, Dalian Maritime University, Dalian, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D000077338:Latanoprost; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D010766:Phosphorylation; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology*; D058475:Tenon Capsule / Q000166:cytology*
chemical_list: D000959:Antihypertensive Agents; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011461:Prostaglandins F, Synthetic; D000072000:NF-KappaB Inhibitor alpha; D000077338:Latanoprost; D020928:Mitogen-Activated Protein Kinases