TRPV1 deletion enhances local inflammation and accelerates the onset of systemic inflammatory response syndrome.

Abstract

The transient receptor potential vanilloid 1 (TRPV1) is primarily localized to sensory nerve fibers and is associated with the stimulation of pain and inflammation. TRPV1 knockout (TRPV1KO) mice show enhanced LPS-induced sepsis compared with wild type (WT). This implies that TRPV1 may have a key modulatory role in increasing the beneficial and reducing the harmful components in sepsis. We investigated immune and inflammatory mechanisms in a cecal ligation and puncture (CLP) model of sepsis over 24 h. CLP TRPV1KO mice exhibited significant hypothermia, hypotension, and organ dysfunction compared with CLP WT mice. Analysis of the inflammatory responses at the site of initial infection (peritoneal cavity) revealed that CLP TRPV1KO mice exhibited: 1) decreased mononuclear cell integrity associated with apoptosis, 2) decreased macrophage tachykinin NK(1)-dependent phagocytosis, 3) substantially decreased levels of nitrite (indicative of NO) and reactive oxygen species, 4) increased cytokine levels, and 5) decreased bacteria clearance when compared with CLP WT mice. Therefore, TRPV1 deletion is associated with impaired macrophage-associated defense mechanisms. Thus, TRPV1 acts to protect against the damaging impact of sepsis and may influence the transition from local to a systemic inflammatory state.

• Authors: Elizabeth S Fernandes, Lihuan Liang, Sarah-Jane Smillie, Frank Kaiser, Robert Purcell, Damian W Rivett, Saydul Alam, Sarah Howat, Helen Collins, Stephen J Thompson, Julie E Keeble, Yanira Riffo-Vasquez, Kenneth D Bruce, Susan D Brain
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 11 Pg. 5741-51 (Jun 01 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22547700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• TRPV Cation Channels
• TRPV1 protein, mouse
• Nitric Oxide

Topics

• Animals
• Female
• Male
• Mice
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Knockout
• Nitric Oxide (antagonists & inhibitors)
• Peritoneum (immunology, pathology, surgery)
• Reactive Oxygen Species (antagonists & inhibitors)
• Systemic Inflammatory Response Syndrome (genetics, immunology, pathology)
• TRPV Cation Channels (biosynthesis, deficiency, genetics)
• Up-Regulation (genetics, immunology)