Polarized Secretion of Interleukin (IL)-6 and IL-8 by Human Airway Epithelia 16HBE14o- Cells in Response to Cationic Polypeptide Challenge

Abstract

BackgroundThe airway epithelium participates in asthmatic inflammation in many ways. Target cells of the epithelium can respond to a variety of inflammatory mediators and cytokines. Damage to the surface epithelium occurs following the secretion of eosinophil-derived, highly toxic cationic proteins. Moreover, the surface epithelium itself is responsible for the synthesis and release of cytokines that cause the selective recruitment, retention, and accumulation of various inflammatory cells. To mimic the damage seen during asthmatic inflammation, the bronchial epithelium can be challenged with highly charged cationic polypeptides such as poly-l-arginine.Methodology/Principal FindingsIn this study, human bronchial epithelial cells, 16HBE14o- cells, were “chemically injured” by exposing them to poly-l-arginine as a surrogate of the eosinophil cationic protein. Cytokine antibody array data showed that seven inflammatory mediators were elevated out of the 40 tested, including marked elevation in interleukin (IL)-6 and IL-8 secretion. IL-6 and IL-8 mRNA expression levels were elevated as measured with real-time PCR. Cell culture supernatants from apical and basolateral compartments were collected, and the IL-6 and IL-8 production was quantified with ELISA. IL-6 and IL-8 secretion by 16HBE14o- epithelia into the apical compartment was significantly higher than that from the basolateral compartment. Using specific inhibitors, the production of IL-6 and IL-8 was found to be dependent on p38 MAPK, ERK1/2 MAPK, and NF-κB pathways.Conclusions/SignificanceThe results clearly demonstrate that damage to the bronchial epithelia by poly-l-arginine stimulates polarized IL-6 and IL-8 secretion. This apically directed secretion of cytokines may play an important role in orchestrating epithelial cell responses to inflammation.

Polarised bovine endometrial epithelial cells vectorially secrete prostaglandins and chemotactic factors under physiological and pathological conditions

“…Directed release of IL8 has been previously reported in human bronchial polarised epithelial cells (Chow et al 2010, Kanoh et al 2011. In this study, and in a previous report describing human bronchial epithelia (Kanoh et al 2011), apical LPS treatment increased IL8 accumulation in the apical and basolateral compartment, whereas basolateral LPS treatment elevated only basolateral IL8 accumulation.…”

Cordyceps Extracts and the Major Ingredient, Cordycepin: Possible Cellular Mechanisms of Their Therapeutic Effects on Respiratory Disease

“…Therefore, this stimulatory effect of CM extract and cordycepin on major secretory cell types of the upper airways may account for its traditional use in treating different respiratory diseases. Our previous study suggests that 16HBE14o-cells can secrete interleukin-(IL-) 6 and IL-8, two important pro-inflammatory cytokines, towards the mucosal side in a polarized fashion (Chow et al, 2010). This phenomenon may contribute to the pathophysiology of asthmatic inflammation and the development of other inflammatory lung diseases (Chow et al, 2010).…”

“…Our previous study suggests that 16HBE14o-cells can secrete interleukin-(IL-) 6 and IL-8, two important pro-inflammatory cytokines, towards the mucosal side in a polarized fashion (Chow et al, 2010). This phenomenon may contribute to the pathophysiology of asthmatic inflammation and the development of other inflammatory lung diseases (Chow et al, 2010). Therefore, the therapeutic effects of CM and cordycepin on airway diseases may be attributed to their influences on immune response regulation (Das et al, 2010), although the detailed molecular mechanisms await to be elucidated.…”

Soy isoflavones improves endometrial barrier through tight junction gene expression

“…In respiratory epithelia, the release of TNFa and IL8, which is mediated by NF-kB, p38MAPK, and ERK1/2 MAPK, has been indicated to relate with the decreased expression of some TJ proteins, i.e. claudin-5 and ZO1, causing an increase in epithelial permeability (Chow et al 2010). This similar mechanism may apply to the downregulation of claudin-8 by LPS in the PEG cells.…”