Abstract
We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H
2S), which plays a key role in the pathogenesis of acute pancreatitis (AP). H
2S-dependent induction of inflammation is mediated by the activation of transcription factor NF-κB. We now provide evidence that activation of Src family kinases (SFKs) is crucial in signaling H
2S-induced intracellular adhesion molecule (ICAM)-1 expression via NF-κB. Stimulation of acini with H
2S resulted in a time-dependent activation of SFKs. In order to better understand this effect of H
2S, acinar cells were stimulated with caerulein after addition of H
2S donor, NaHS. Inhibition of SFKs impaired H
2S-induced NF-κB activity and ICAM-1 expression in caerulein treated acinar cells. We also observed that H
2S-induced up-regulation of ICAM-1 enhanced the adhesion of neutrophils onto acinar cells. Analysis of NF-κB pathway revealed that the effect of SFKs inhibition correlated with IκBα degradation and NF-κB DNA binding function. Interestingly, H
2S-induced association of SFKs with translocation of NF-κB, and inhibition of SFKs prevented this response, indicating that this interaction may depend on activation of SFKs. These data suggest that H
2S, by activating the phosphorylation of SFKs, may promote the transcriptional activity of NF-κB and eventually lead to an upregulation of ICAM-1 expression.