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Role of substance P in hydrogen sulfide-induced pulmonary inflammation in mice.
Bhatia, Madhav; Zhi, Liang; Zhang, Huili; Ng, Siaw-Wei; Moore, Philip K.
Afiliação
  • Bhatia 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
Am J Physiol Lung Cell Mol Physiol ; 291(5): L896-904, 2006 Nov.
Article em En | MEDLINE | ID: mdl-16798781
ABSTRACT
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.
Assuntos
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Base de dados: MEDLINE Assunto principal: Pneumonia / Substância P / Poluentes Atmosféricos / Sulfeto de Hidrogênio Idioma: En Ano de publicação: 2006 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Pneumonia / Substância P / Poluentes Atmosféricos / Sulfeto de Hidrogênio Idioma: En Ano de publicação: 2006 Tipo de documento: Article