Abstract
Inflammatory bowel disease of the colon is associated with a high osmolarity of colonic contents. We hypothesized that this hyperosmolarity may contribute to colonic inflammation by stimulating the proinflammatory activity of intestinal epithelial cells (IECs). The human IEC lines HT-29 and Caco-2 were used to study the effect of hyperosmolarity on the IEC inflammatory response. Exposure of IECs to hyperosmolarity triggered expression of the proinflammatory chemokine interleukin (IL)-8 both at the secreted protein and mRNA levels. In addition, hyperosmotic stimulation induced the release of another chemokine, GRO-α. These effects were because of activation of the transcription factor, nuclear factor (NF)-κB, because hyperosmolarity stimulated both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Hyperosmolarity activated both p38 and p42/44 mitogen-activated protein kinases, which effect contributed to hyperosmolarity-stimulated IL-8 production, because p38 and p42/44 inhibition prevented the hyperosmolarity-induced increase in IL-8 production. In addition, the proinflammatory effects of hyperosmolarity were, in a large part, mediated by activation of Na+/H+ exchangers, because selective blockade of Na+/H+ exchangers prevented the hyperosmolarity-induced IEC inflammatory response. In summary, hyperosmolarity stimulates IEC IL-8 production, which effect may contribute to the maintenance of inflammation in inflammatory bowel disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 987-996 |
| Number of pages | 10 |
| Journal | American Journal of Pathology |
| Volume | 161 |
| Issue number | 3 |
| State | Published - Sep 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Hyperosmotic stress induces nuclear factor-κB activation and interleukin-8 production in human intestinal epithelial cells. / Németh, Zoltán H.; Deitch, Edwin A.; Szabo, Csaba; Haskó, György.
In: American Journal of Pathology, Vol. 161, No. 3, 09.2002, p. 987-996.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hyperosmotic stress induces nuclear factor-κB activation and interleukin-8 production in human intestinal epithelial cells
AU - Németh, Zoltán H.
AU - Deitch, Edwin A.
AU - Szabo, Csaba
AU - Haskó, György
PY - 2002/9
Y1 - 2002/9
N2 - Inflammatory bowel disease of the colon is associated with a high osmolarity of colonic contents. We hypothesized that this hyperosmolarity may contribute to colonic inflammation by stimulating the proinflammatory activity of intestinal epithelial cells (IECs). The human IEC lines HT-29 and Caco-2 were used to study the effect of hyperosmolarity on the IEC inflammatory response. Exposure of IECs to hyperosmolarity triggered expression of the proinflammatory chemokine interleukin (IL)-8 both at the secreted protein and mRNA levels. In addition, hyperosmotic stimulation induced the release of another chemokine, GRO-α. These effects were because of activation of the transcription factor, nuclear factor (NF)-κB, because hyperosmolarity stimulated both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Hyperosmolarity activated both p38 and p42/44 mitogen-activated protein kinases, which effect contributed to hyperosmolarity-stimulated IL-8 production, because p38 and p42/44 inhibition prevented the hyperosmolarity-induced increase in IL-8 production. In addition, the proinflammatory effects of hyperosmolarity were, in a large part, mediated by activation of Na+/H+ exchangers, because selective blockade of Na+/H+ exchangers prevented the hyperosmolarity-induced IEC inflammatory response. In summary, hyperosmolarity stimulates IEC IL-8 production, which effect may contribute to the maintenance of inflammation in inflammatory bowel disease.
AB - Inflammatory bowel disease of the colon is associated with a high osmolarity of colonic contents. We hypothesized that this hyperosmolarity may contribute to colonic inflammation by stimulating the proinflammatory activity of intestinal epithelial cells (IECs). The human IEC lines HT-29 and Caco-2 were used to study the effect of hyperosmolarity on the IEC inflammatory response. Exposure of IECs to hyperosmolarity triggered expression of the proinflammatory chemokine interleukin (IL)-8 both at the secreted protein and mRNA levels. In addition, hyperosmotic stimulation induced the release of another chemokine, GRO-α. These effects were because of activation of the transcription factor, nuclear factor (NF)-κB, because hyperosmolarity stimulated both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Hyperosmolarity activated both p38 and p42/44 mitogen-activated protein kinases, which effect contributed to hyperosmolarity-stimulated IL-8 production, because p38 and p42/44 inhibition prevented the hyperosmolarity-induced increase in IL-8 production. In addition, the proinflammatory effects of hyperosmolarity were, in a large part, mediated by activation of Na+/H+ exchangers, because selective blockade of Na+/H+ exchangers prevented the hyperosmolarity-induced IEC inflammatory response. In summary, hyperosmolarity stimulates IEC IL-8 production, which effect may contribute to the maintenance of inflammation in inflammatory bowel disease.
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UR - http://www.scopus.com/inward/citedby.url?scp=0036735192&partnerID=8YFLogxK
M3 - Article
VL - 161
SP - 987
EP - 996
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -