title: Human lung fibroblasts express interleukin-6 in response to signaling after mast cell contact.
abstract: Asthma is a chronic inflammatory disease of the airways. Mast cell-derived cytokines may mediate both airway inflammation and remodeling. It has also been shown that fibroblasts can be the source of proinflammatory cytokines. In the human airways, mast cell-fibroblast interactions may have pivotal effects on modulating inflammation. To study this further, we cocultured normal human lung fibroblasts (NHLF) with a human mast cell line (HMC-1) and assayed for production of interleukin (IL)-6, an important proinflammatory cytokine. When cultured together, NHLF/HMC-1 contact induced IL-6 secretion. Separation of HMC-1 and NHLF cells by a porous membrane inhibited this induction. HMC-1-derived cellular membranes caused an increase in IL-6 production in NHLF. Activation of p38 MAPK was also seen in cocultures by Western blot, whereas IL-6 production in cocultures was significantly inhibited by the p38 inhibitor SB203580. IL-6 production in cocultures was minimally inhibited by a chemical inhibitor of nuclear factor-kappaB (Bay11), indicating that nuclear factor-kappaB may have a minimal role in signaling IL-6 production in mast cell/fibroblasts cocultures. Blockade of inter-cellular adhesion molecule-1, tumor necrosis factor-RI, and surface IL-1beta with neutralizing antibodies failed to significantly decrease IL-6 production in our coculture, indicating that other receptor-ligand associations may be responsible for this activation. These novel studies reveal the importance of cell-cell interactions in the complex milieu of airway inflammation.
authors.affiliation: Department of Internal Medicine, East Tennessee State University, Johnson City, TN 37614, USA. mattfitzgerald1@aol.com
authors.forename: S Matthew
authors.initials: SM
authors.lastname: Fitzgerald
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lee
authors.forename: H Kenton
authors.initials: HK
authors.lastname: Hall
authors.forename: David S
authors.initials: DS
authors.lastname: Chi
authors.forename: Guha
authors.initials: G
authors.lastname: Krishnaswamy
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003907:Dexamethasone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology* / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D015850:Interleukin-6; D016328:NF-kappa B; D009570:Nitriles; D011725:Pyridines; D013450:Sulfones; D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580