Is inflammation a consequence of extracellular hyperosmolarity?

Abstract

BackgroundThere are several reports suggesting that hyperosmolarity induces inflammation. We recently showed that Dextran Sodium Sulfate causes inflammatory bowel disease due to hyperosmolarity. The aim of this study was to confirm the link between hyperosmolarity and inflammation by assessing osmolarity values in vivo during inflammation, compare the inflammatory potential of different osmotic agents and finally study the long-term consequences of hyperosmolarity on cell fate.MethodsOsmotic pressures were measured in inflammatory liquids withdrawn from mice subjected to inflammation caused either by subcutaneous injection of Bacille Calmette-Guérin (BCG) or Freund adjuvant. Three epithelial cell lines (HT29, T24 and A549) were exposed up to 48 hours to increasing osmolarities (300, 600, 900 mOsm) of chemically inert molecules such as Mannitol, Propylene Glycol, and Glycerol and inflammatory response was assessed by Enzyme Linked ImmunoSorbent Assay (ELISA) and RNA Protection Assay (RPA). Finally, normal mouse macrophages were exposed to hyperosmotic conditions for long-term culture.ResultsThe inflammation caused either by BCG or Freund adjuvant is correlated to hyperosmolarity in inflammatory liquids. The exposure of cells to the different compounds, whatever their molecular weight, has no effect on the secretion of cytokines as long as the osmolarity is below a threshold of 300 mOsm. Higher osmolarities result in the secretion of proinflammatory cytokines (Interleukin-8, Interleukin-6, Interleukin-1β and Tumor Necrosis factor-α). Long-term hyperosmotic culture extends normal macrophage half-life, from 44 days to 102 days, and alters the expression of p53, Bcl-2 and Bax.ConclusionThe present study further suggests inflammation and hyperosmolarity are closely related phenomena if not synonymous.

Protein Kinase R Mediates the Inflammatory Response Induced by Hyperosmotic Stress

“…It has been previously hypothesized that DSS contributes to induction of colitis via a hyperosmotic stress response (50,53). Here, we provide direct evidence that DSS increases the osmolarity of extracellular fluid and that osmoadaptive genes are upregulated in response to DSS-induced extracellular osmolarities of 395 mosM.…”

“…However, the signaling pathway leading from DSS treatment to iNOS induction via PKR may not be the same as detailed above in the hyperosmotic stress response. Although DSS has been suggested to increase the extracellular osmolarity (50,53), the molecular mechanisms of the cellular response to DSS are not well studied. In order to investigate the hypothesis that DSS induces a hyperosmotic stress response sufficient to cause colitis, we used a culture model of MEF cells treated directly with DSS as a hyperosmotic agent.…”

Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2

“…LD formation is not an event relevant only for our cellular model, but could have implications in other systems as well. Schwartz et al ( 37 ) revealed that pathogen-related infl ammatory reaction increases the osmolarity of infl ammatory fl uids. Given that infl ammation is an essential cellular response to all stress inducers, its intimate connection with HO becomes an important issue in contexts different from that of the corneal surface or DES.…”

A combination of alpha lipoic acid and calcium hydroxycitrate is efficient against mouse cancer models: Preliminary results

“…Just as there is now considerable ONCOLOGY REPORTS 23: 1407-1416, 2010 A combination of alpha lipoic acid and calcium hydroxycitrate is efficient against mouse cancer models: Preliminary results interest in the role of the glycolytic phenotype as a key target for the development of effective drugs for cancer, the inflammatory response has also been recognized as a potential target (12,13). Our laboratory has in the past few years investigated the role of hyperosmolarity as a cause of inflammation and its potential link to cancer (14)(15)(16) and most recently showed that the inhalation of carbon dioxide, a product of cellular respiration, was able to induce inflammation of the lung (17). As a consequence, focusing on metabolic changes involving glucose metabolism that characterize cancer cells appeared to us to be a logical extension of our work in the area of inflammation.…”