title: Differential chemokine regulation by Th2 cytokines during human RPE-monocyte coculture.
abstract: OBJECTIVE
  To determine the effects of the potent anti-inflammatory Th2 cytokines, interleukin (IL)-4, -10, and -13, on IL-8 and monocyte chemoattractant protein (MCP) 1 production by human retinal pigment epithelial (HRPE) cells, monocytes, and HRPE cell-monocyte cocultures.
  
  
  METHODS
  Enzyme-linked immunosorbent assays were performed to determine IL-8 and MCP-1 secretion by HRPE cells, monocytes, and HRPE cell-monocyte cocultures stimulated with IL-1beta or TNF-alpha, either alone, or in combination with IL-4, -10, or -13, at various time points.
  
  
  RESULTS
  IL-4 and -13, but not IL-10, enhanced constitutive and TNF-alpha-induced HRPE IL-8 and MCP-1 secretion. IL-4 also enhanced IL-1beta-induced HRPE IL-8. IL-4 and -13 reduced monocyte IL-8 and MCP-1, whereas IL-10 reduced monocyte IL-8 but enhanced MCP-1. Overlay of monocytes onto HRPE cell cultures resulted in increased IL-8 and MCP-1 secretion. IL-8 secretion by HRPE cell-monocyte cocultures was inhibited by IL-4, -10, and -13, whereas MCP-1 was inhibited only by IL-10. These cytokines also inhibited IL-1beta potentiation of IL-8, but not MCP-1 secretion by cocultures. IL-4 enhanced TNF-alpha potentiation of chemokine secretion by cocultures, whereas IL-10 had no effects. IL-13 potentiated TNF-alpha-induced MCP-1, but not IL-8 secretion by cocultures.
  
  
  CONCLUSIONS
  IL-4, -10 and -13 have complex effects on chemokine secretion by HRPE cells, monocytes, and HRPE cell-monocyte cocultures. IL-10 appears to be the most consistently suppressive cytokine, suggesting potential therapeutic usefulness of IL-10 in the treatment of ocular inflammatory and proliferative diseases.
authors.affiliation: Department of Ophthalmology, University of Michigan, Ann Arbor 48105, USA.
authors.forename: A
authors.initials: A
authors.lastname: Yoshida
authors.forename: S G
authors.initials: SG
authors.lastname: Elner
authors.forename: Z M
authors.initials: ZM
authors.lastname: Bian
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: N W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: V M
authors.initials: VM
authors.lastname: Elner
mesh_terms: D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics; D018920:Coculture Techniques; D016207:Cytokines / Q000494:pharmacology*; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D004338:Drug Combinations; D007375:Interleukin-1; D018793:Interleukin-13; D016209:Interleukin-8; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4