Inhibition of hydrogen sulfide synthesis attenuates chemokine production and protects mice against acute pancreatitis and associated lung injury.
OBJECTIVE
The present study investigated whether chemokines are involved in hydrogen sulfide (H2S)-associated pathogenesis of acute pancreatitis and associated lung injury.


METHODS
We have examined the effect of DL-propargylglycine, a cystathionine gamma-lyase inhibitor, on the synthesis of CC chemokine monocyte chemotactic protein 1, Regulated upon Activation, Normal T-cell Expressed, and Secreted, and macrophage inflammatory protein-1alpha (MIP-1alpha), and CXC chemokine MIP-2 in an in vitro and in vivo model of cerulein-induced acute pancreatitis and associated lung injury. In addition, the pancreatic acinar cells were treated with H2S donor drug, sodium hydrosulfide. The expression of these chemokines in the pancreatic acini, pancreas, and lungs was determined by quantitative real-time reverse transcriptase polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemistry.


RESULTS
After treatment with DL-propargylglycine, reverse transcriptase polymerase chain reaction, and enzyme-linked immunosorbent assay demonstrated down-regulation of cerulein-induced increase in monocyte chemotactic protein 1, MIP-1alpha, and MIP-2 expression but had no apparent effect on Regulated upon Activation, Normal T-cell Expressed, and Secreted expression.


CONCLUSIONS
These results suggest that the proinflammatory effect of H2S may be mediated by chemokines.
Tamizhselvi
Ramasamy
R
Department of Pharmacology, National University of Singapore, Singapore.
Moore
Philip K
PK
Bhatia
Madhav
M
D000208:Acute Disease; D000480:Alkynes / Q000627:therapeutic use*; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology / Q000633:toxicity; D018946:Chemokine CCL5 / Q000235:genetics; D018925:Chemokines / Q000037:antagonists & inhibitors*; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors; D017931:DNA Primers; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006862:Hydrogen Sulfide / Q000009:adverse effects*; D008297:Male; D051379:Mice; D010195:Pancreatitis / Q000139:chemically induced / Q000517:prevention & control*; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000480:Alkynes; D018946:Chemokine CCL5; D018925:Chemokines; D017931:DNA Primers; C009055:propargylglycine; D002108:Ceruletide; D003542:Cystathionine gamma-Lyase; D005998:Glycine; D006862:Hydrogen Sulfide