Human Lung Fibroblasts Express Interleukin-6 in Response to Signaling After Mast Cell Contact
Document Type
Article
Publication Date
4-1-2004
Description
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-κB (Bay11), indicating that nuclear factor-κB may have a minimal role in signaling IL-6 production in mast cell/fibroblasts cocultures. Blockade of intercellular adhesion molecule-1, tumor necrosis factor-RI, and surface IL-1β 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.
Citation Information
Fitzgerald, S. Matthew; Lee, Steven A.; Hall, H. Kenton; Chi, David S.; and Krishnaswamy, Guha. 2004. Human Lung Fibroblasts Express Interleukin-6 in Response to Signaling After Mast Cell Contact. American Journal of Respiratory Cell and Molecular Biology. Vol.30(4). 585-593. https://doi.org/10.1165/rcmb.2003-0282OC PMID: 14565941 ISSN: 1044-1549