| Abstract | Hydrogen sulfide (H2S) has been shown to induce the activation of neurogenic inflammation especially in normal airways and urinary bladder. However, whether endogenous H2S would regulate sepsis-associated lung inflammation via substance P (SP) and its receptors remains unknown. Therefore, the aim of the study was to investigate the effect of H2S on the pulmonary level of SP in cecal ligation and puncture (CLP)-induced sepsis and its relevance to lung injury. Male Swiss mice or male preprotachykinin-A gene knockout (PPT-A-/-) mice and their wild-type (PPT-A+/+) mice were subjected to CLP-induced sepsis. DL-propargylglycine (50 mg/kg i.p.), an inhibitor of H2S formation was administered either 1 h before or 1 h after the induction of sepsis, while NaHS, an H2S donor, was given at the same time as CLP. L703606, an inhibitor of the neurokinin-1 receptor was given 30 min before CLP. DL-propargylglycine pretreatment or posttreatment significantly decreased the PPT-A gene expression and the production of SP in lung whereas administration of NaHS resulted in a further rise in the pulmonary level of SP in sepsis. PPT-A gene deletion and pretreatment with L703606 prevented H2S from aggravating lung inflammation. In addition, septic mice genetically deficient in PPT-A gene or pretreated with L703606 did not exhibit further increase in lung permeability after injection of NaHS. The present findings show for the first time that in sepsis, H2S up-regulates the generation of SP, which contributes to lung inflammation and lung injury mainly via activation of the neurokinin-1 receptor. |
| Authors | Huili Zhang, Akhil Hegde, Siaw Wei Ng, Sharmila Adhikari, Shabbir M Moochhala, Madhav Bhatia
(Affiliation: Department of Pharmacology, National University of Singapore, Singapore, Singapore.)
|
| Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 179
Issue 6
Pg. 4153-60
(Sep 15 2007)
ISSN: 0022-1767 United States |
| PMID | 17785854
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Inflammation Mediators
- Protein Precursors
- Quinuclidines
- Receptors, Neurokinin-1
- Sulfides
- Tachykinins
- preprotachykinin
- L 703606
- sodium bisulfide
- Substance P
- Hydrogen Sulfide
|
| Topics |
- Animals
- Cecum
(surgery)
- Gene Deletion
- Hydrogen Sulfide
(antagonists & inhibitors, metabolism, pharmacology)
- Inflammation Mediators
(antagonists & inhibitors, metabolism, pharmacology)
- Ligation
- Lung
(drug effects, metabolism, microbiology, pathology)
- Male
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Protein Precursors
(deficiency, genetics)
- Punctures
- Quinuclidines
(administration & dosage, therapeutic use)
- Receptors, Neurokinin-1
(antagonists & inhibitors)
- Sepsis
(drug therapy, genetics, metabolism, microbiology)
- Substance P
(biosynthesis)
- Sulfides
(administration & dosage)
- Tachykinins
(deficiency, genetics)
- Up-Regulation
(drug effects)
|
