Published ahead of print on October 17, 2003, doi:10.1165/rcmb.2003-0282OC Am. J. Respir. Cell Mol. Biol., Volume 30, Number 4, April 2004, 585-593 A more recent version of this article appeared on April 1, 2004
Submitted on July 28, 2003 Human Lung Fibroblasts Express IL-6 in Response to Signaling Following Mast Cell ContactSteven Matthew Fitzgerald1*,1 Internal Medicine, East Tennessee State University, Johnson City, Tennessee, USA * To whom correspondence should be addressed. E-mail: mattfitzgerald1{at}aol.com.
Asthma is a chronic inflammatory disease of the airways. Mast cell derived cytokines may mediate both airway inflammation as well as 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 interleukin-6 (IL-6) production, 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 while IL-6 production in cocultures was significantly inhibited be the p38 inhibitor SB203580. IL-6 production in cocultures was minimally inhibited by a chemical inhibitor of NF-
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B (Bay11) indicating that NF-
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.
