Hydrogen sulfide induces ICAM-1 expression and neutrophil adhesion to caerulein-treated pancreatic acinar cells through NF-kappaB and Src-family kinases pathway.
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.
Tamizhselvi
Ramasamy
R
Department of Pharmacology, National University of Singapore, Singapore, Singapore.
Koh
Yung-Hua
YH
Sun
Jia
J
Zhang
Huili
H
Bhatia
Madhav
M
D000393:Air Pollutants / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D002108:Ceruletide / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D000393:Air Pollutants; D016328:NF-kappa B; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D002108:Ceruletide; D019061:src-Family Kinases; D006862:Hydrogen Sulfide