TY - JOUR
T1 - TRPV1 deletion enhances local inflammation and accelerates the onset of systemic inflammatory response syndrome
AU - Fernandes, Elizabeth S.
AU - Liang, Lihuan
AU - Smillie, Sarah Jane
AU - Kaiser, Frank
AU - Purcell, Robert
AU - Rivett, Damian W.
AU - Alam, Saydul
AU - Howat, Sarah
AU - Collins, Helen
AU - Thompson, Stephen J.
AU - Keeble, Julie E.
AU - Riffo-Vasquez, Yanira
AU - Bruce, Kenneth D.
AU - Brain, Susan D.
PY - 2012/6/1
Y1 - 2012/6/1
N2 - 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 NK1-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. Copyright
AB - 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 NK1-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. Copyright
UR - http://www.scopus.com/inward/record.url?scp=84862098500&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1102147
DO - 10.4049/jimmunol.1102147
M3 - Journal articles
C2 - 22547700
AN - SCOPUS:84862098500
SN - 0022-1767
VL - 188
SP - 5741
EP - 5751
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -