Role of substance P in hydrogen sulfide-induced pulmonary inflammation in mice.
We have shown earlier that H(2)S acts as a mediator of inflammation. In this study, we have investigated the involvement of substance P and neurogenic inflammation in H(2)S-induced lung inflammation. Intraperitoneal administration of NaHS (1-10 mg/kg), an H(2)S donor, to mice caused a significant increase in circulating levels of substance P in a dose-dependent manner. H(2)S alone could also cause lung inflammation, as evidenced by a significant increase in lung myeloperoxidase activity and histological evidence of lung injury. The maximum effect of H(2)S on substance P levels and on lung inflammation was observed 1 h after NaHS administration. At this time, a significant increase in lung levels of TNF-alpha and IL-1beta was also observed. In substance P-deficient mice, the preprotachykinin-A knockout mice, H(2)S did not cause any lung inflammation. Furthermore, pretreatment of mice with CP-96345 (2.5 mg/kg ip), an antagonist of the neurokinin-1 (NK(1)) receptor, protected mice against lung inflammation caused by H(2)S. However, treatment with antagonists of NK(2), NK(3), and CGRP receptors did not have any effect on H(2)S-induced lung inflammation. Depleting neuropeptide from sensory neurons by capsaicin (50 mg/kg sc) significantly reduced the lung inflammation caused by H(2)S. In addition, pretreatment of mice with capsazepine (15 mg/kg sc), an antagonist of the transient receptor potential vanilloid-1, protected mice against H(2)S-induced lung inflammation. These results demonstrate a key role of substance P and neurogenic inflammation in H(2)S-induced lung injury in mice.
Bhatia
Madhav
M
Department of Pharmacology, National University of Singapore, Yong Loo Lin School of Medicine, Bldg. MD2, 18 Medical Dr., Singapore 117597. mbhatia@nus.edu.sg
Zhi
Liang
L
Zhang
Huili
H
Ng
Siaw-Wei
SW
Moore
Philip K
PK
D000393:Air Pollutants / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006862:Hydrogen Sulfide / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D018836:Inflammation Mediators / Q000276:immunology / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000294:innervation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D064729:Neurokinin-1 Receptor Antagonists; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D013373:Substance P / Q000276:immunology* / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism
D000393:Air Pollutants; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D018836:Inflammation Mediators; D064729:Neurokinin-1 Receptor Antagonists; D011498:Protein Precursors; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D009195:Peroxidase; C071423:capsazepine; D002211:Capsaicin; C066892:CP 96345; D006862:Hydrogen Sulfide