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Rac1 signaling regulates neutrophil-dependent tissue damage in experimental colitis.

Changhui, Yu LU ; Zhang, Su LU ; Song, Lei LU ; Wang, Yusheng LU ; Hwaiz, Rundk LU ; Luo, Lingtao and Thorlacius, Henrik LU (2014) In European Journal of Pharmacology 741(Jul 30). p.90-96
Abstract
Excessive neutrophil recruitment in the colon is a major feature in acute colitis although the signaling mechanisms behind colonic recruitment of neutrophils remain elusive. Herein, we hypothesized that Rac1 activity might play an important role in neutrophil infiltration in the inflamed colon. Female Balb/c mice were treated with the Rac1 inhibitor NSC23766 (0.5 and 5mg/kg) before and daily after administration of 5% dextran sodium sulfate (DSS). Colonic tissue was collected for quantification of neutrophil recruitment, interleukin-6 (IL-6) and CXC chemokine formation as well as histological damage score five days after challenge with DSS. Rac1 activity was determined by western blot and Mac-1 expression by flow cytometry in neutrophils.... (More)
Excessive neutrophil recruitment in the colon is a major feature in acute colitis although the signaling mechanisms behind colonic recruitment of neutrophils remain elusive. Herein, we hypothesized that Rac1 activity might play an important role in neutrophil infiltration in the inflamed colon. Female Balb/c mice were treated with the Rac1 inhibitor NSC23766 (0.5 and 5mg/kg) before and daily after administration of 5% dextran sodium sulfate (DSS). Colonic tissue was collected for quantification of neutrophil recruitment, interleukin-6 (IL-6) and CXC chemokine formation as well as histological damage score five days after challenge with DSS. Rac1 activity was determined by western blot and Mac-1 expression by flow cytometry in neutrophils. Administration of NSC23766 decreased DSS-induced neutrophil recruitment and tissue damage in the colon. Rac1 inhibition decreased colonic formation of IL-6 and CXC chemokines in experimental colitis. Chemokine challenge increased Rac1 activity in neutrophils and NSC23766 markedly reduced this neutrophil activity of Rac1. Inhibition of Rac1 abolished CXC chemokine-induced neutrophil chemotaxis and up-regulation of Mac-1 in vitro. Taken together, Rac1 signaling plays a significant role in controlling accumulation of neutrophils and tissue injury in experimental colitis. Thus, our novel results suggest that targeting Rac1 signaling might be a useful way to protect against neutrophil-mediated tissue injury in acute colitis. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
741
issue
Jul 30
pages
90 - 96
publisher
Elsevier
external identifiers
  • pmid:25084221
  • wos:000343140600011
  • scopus:84906962260
ISSN
1879-0712
DOI
10.1016/j.cjphar.2014.07.039
language
English
LU publication?
yes
id
910f0710-a91a-4269-85ae-b4e495403111 (old id 4615727)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25084221?dopt=Abstract
date added to LUP
2014-09-03 20:03:50
date last changed
2017-01-01 03:19:14
@article{910f0710-a91a-4269-85ae-b4e495403111,
  abstract     = {Excessive neutrophil recruitment in the colon is a major feature in acute colitis although the signaling mechanisms behind colonic recruitment of neutrophils remain elusive. Herein, we hypothesized that Rac1 activity might play an important role in neutrophil infiltration in the inflamed colon. Female Balb/c mice were treated with the Rac1 inhibitor NSC23766 (0.5 and 5mg/kg) before and daily after administration of 5% dextran sodium sulfate (DSS). Colonic tissue was collected for quantification of neutrophil recruitment, interleukin-6 (IL-6) and CXC chemokine formation as well as histological damage score five days after challenge with DSS. Rac1 activity was determined by western blot and Mac-1 expression by flow cytometry in neutrophils. Administration of NSC23766 decreased DSS-induced neutrophil recruitment and tissue damage in the colon. Rac1 inhibition decreased colonic formation of IL-6 and CXC chemokines in experimental colitis. Chemokine challenge increased Rac1 activity in neutrophils and NSC23766 markedly reduced this neutrophil activity of Rac1. Inhibition of Rac1 abolished CXC chemokine-induced neutrophil chemotaxis and up-regulation of Mac-1 in vitro. Taken together, Rac1 signaling plays a significant role in controlling accumulation of neutrophils and tissue injury in experimental colitis. Thus, our novel results suggest that targeting Rac1 signaling might be a useful way to protect against neutrophil-mediated tissue injury in acute colitis.},
  author       = {Changhui, Yu and Zhang, Su and Song, Lei and Wang, Yusheng and Hwaiz, Rundk and Luo, Lingtao and Thorlacius, Henrik},
  issn         = {1879-0712},
  language     = {eng},
  number       = {Jul 30},
  pages        = {90--96},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Rac1 signaling regulates neutrophil-dependent tissue damage in experimental colitis.},
  url          = {http://dx.doi.org/10.1016/j.cjphar.2014.07.039},
  volume       = {741},
  year         = {2014},
}