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Hydrogen sulfide induces ICAM-1 expression and neutrophil adhesion to caerulein-treated pancreatic acinar cells through NF-kappaB and Src-family kinases pathway.
- Source :
-
Experimental cell research [Exp Cell Res] 2010 May 15; Vol. 316 (9), pp. 1625-36. Date of Electronic Publication: 2010 Mar 06. - Publication Year :
- 2010
-
Abstract
- We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H(2)S), which plays a key role in the pathogenesis of acute pancreatitis (AP). H(2)S-dependent induction of inflammation is mediated by the activation of transcription factor NF-kappaB. We now provide evidence that activation of Src family kinases (SFKs) is crucial in signaling H(2)S-induced intracellular adhesion molecule (ICAM)-1 expression via NF-kappaB. Stimulation of acini with H(2)S resulted in a time-dependent activation of SFKs. In order to better understand this effect of H(2)S, acinar cells were stimulated with caerulein after addition of H(2)S donor, NaHS. Inhibition of SFKs impaired H(2)S-induced NF-kappaB activity and ICAM-1 expression in caerulein treated acinar cells. We also observed that H(2)S-induced up-regulation of ICAM-1 enhanced the adhesion of neutrophils onto acinar cells. Analysis of NF-kappaB pathway revealed that the effect of SFKs inhibition correlated with IkappaBalpha degradation and NF-kappaB DNA binding function. Interestingly, H(2)S-induced association of SFKs with translocation of NF-kappaB, and inhibition of SFKs prevented this response, indicating that this interaction may depend on activation of SFKs. These data suggest that H(2)S, by activating the phosphorylation of SFKs, may promote the transcriptional activity of NF-kappaB and eventually lead to an upregulation of ICAM-1 expression.<br /> (Copyright 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Air Pollutants pharmacology
Animals
Blotting, Western
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Intercellular Adhesion Molecule-1 genetics
Mice
NF-kappa B genetics
Neutrophils cytology
Pancreas cytology
Pancreas metabolism
Phosphorylation drug effects
RNA, Messenger genetics
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Up-Regulation
src-Family Kinases genetics
Cell Adhesion
Ceruletide pharmacology
Hydrogen Sulfide pharmacology
Intercellular Adhesion Molecule-1 metabolism
NF-kappa B metabolism
Neutrophils metabolism
src-Family Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2422
- Volume :
- 316
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Experimental cell research
- Publication Type :
- Academic Journal
- Accession number :
- 20211170
- Full Text :
- https://doi.org/10.1016/j.yexcr.2010.02.044