Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 290, Issue 3, Pages C678-C690Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00166.2005
Keywords
toll-like receptor; nuclear factor-kappa B; interleukin-8; tumor necrosis factor; interleukin-1
Categories
Funding
- NIADDK NIH HHS [R01-AM-19579, P01-AM-150496] Funding Source: Medline
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We measured innate immune responses by primary human tracheal epithelial (HTE) cells grown as confluent, pseudostratified layers during exposure to inflammatory activators on apical vs. basolateral surfaces. Apical Pseudomonas aeruginosa strain PAK ( but not flagellin mutant PAK center dot fliC), flagellin, and flagellin + PAK center dot fliC activated NF-B-kappa and IL-8 expression and secretion. In contrast, HTE cells were insensitive to LPS compared to flagellin. Flagellin activated NF-B-kappa in columnar but not basal cells. IL-1 beta + TNF-alpha elicited responses similar to those of flagellin. Basolateral flagellin or IL-1 beta + TNF-alpha caused 1.5- to 4-fold larger responses, consistent with the fact that NF-B-kappa activation occurred in both columnar and basal cells. MyD88 (toll receptor-associated adapter), IL-1 receptor (IL1R)1, and TNF-alpha receptor (TNFR)1 were expressed in columnar and basal cells. ZO-1 was localized to tight junctions of columnar cells but not to basal cells. We infer the following. 1) Flagellin is necessary and sufficient to trigger inflammatory responses in columnar cells during accumulation of P. aeruginosa in the airway surface liquid (ASL); columnar cells express toll-like receptor 5 and MyD88, often associated with flagellin-activated cell signaling. 2) IL-1 beta + TNF-alpha in the ASL also activate columnar cells, and these cells also express IL1R1 and TNFR1. 3) Apical flagellin, IL-1 beta, and TNF-alpha do not activate basal cells because tight junctions between columnar cells prevent access from the apical surface to the basal cells. 4) Exposure of basolateral surfaces to inflammatory activators elicits larger responses because both columnar and basal cells are activated, likely because both cell types express receptors for flagellin, IL-1 beta, and TNF-alpha.
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