{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T19:22:02Z","timestamp":1769196122211,"version":"3.49.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>To test the hypothesis that ablation of transient receptor potential vanilloid type 1 (TRPV1) channels leads to exacerbated inflammatory responses and organ damage during endotoxic shock, lipopolysaccharide (LPS; 5 million endotoxin units\/kg of body weight) was injected intraperitoneally (i.p.) into wild-type (WT) and TRPV1-null mutant (TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup>) mice. Mean arterial pressure and heart rate, determined by radiotelemetry, were severely depressed after LPS injection into WT and TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup>mice, with no distinction between the two strains. At 24 h after LPS injection, renal glomerular hypercellularity and hepatocellular injury were observed in both strains, accompanying further elevated serum levels of creatinine and alanine aminotransferase in TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup>mice compared to those in WT mice. At 6 or 24 h after LPS injection, neutrophil recruitment into kidneys and livers, serum cytokine (tumor necrosis factor alpha [TNF-\u03b1], interleukin 1\u03b2 [IL-1\u03b2], IL-6) and renal chemokine (KC, macrophage inflammatory protein 2 [MIP-2]) levels, and renal VCAM-1 and ICAM-1 expression were greater in TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup>mice than WT mice. In addition, increased plasma calcitonin gene-related peptide (CGRP) levels observed in WT mice 6 h after LPS injection were absent in TRPV1<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Thus, TRPV1 ablation aggravates inflammatory responses, including neutrophil infiltration, proinflammatory cytokine production, and adhesion molecule expression, leading to intensified organ damage during endotoxic shock in the absence of worsened circulatory failure. The data indicate that TRPV1 activation may attenuate endotoxin-induced organ damage, possibly via its anti-inflammatory action rather than alteration of hemodynamics.<\/jats:p>","DOI":"10.1128\/cvi.00674-12","type":"journal-article","created":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T07:54:35Z","timestamp":1367481275000},"page":"1008-1015","source":"Crossref","is-referenced-by-count":37,"title":["TRPV1 Ablation Aggravates Inflammatory Responses and Organ Damage during Endotoxic Shock"],"prefix":"10.1128","volume":"20","author":[{"given":"Youping","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donna H.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","published-online":{"date-parts":[[2013,5,1]]},"reference":[{"key":"key20180919073656_B1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1126\/science.288.5464.306","article-title":"Impaired nociception and pain sensation in mice lacking the capsaicin receptor","volume":"288","author":"Caterina","year":"2000","journal-title":"Science"},{"key":"key20180919073656_B2","first-page":"159","article-title":"Vanilloid (capsaicin) receptors and mechanisms","volume":"51","author":"Szallasi","year":"1999","journal-title":"Pharmacol. Rev."},{"key":"key20180919073656_B3","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/22761","article-title":"Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide","volume":"400","author":"Zygmunt","year":"1999","journal-title":"Nature"},{"key":"key20180919073656_B4","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/0140-6736(91)91452-Z","article-title":"Septic shock: pathogenesis","volume":"338","author":"Glauser","year":"1991","journal-title":"Lancet"},{"key":"key20180919073656_B5","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1056\/NEJM199305203282008","article-title":"Pathogenetic mechanisms of septic shock","volume":"328","author":"Parrillo","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"key20180919073656_B6","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1056\/NEJM199901213400307","article-title":"Treating patients with severe sepsis","volume":"340","author":"Wheeler","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"key20180919073656_B7","doi-asserted-by":"crossref","first-page":"H595","DOI":"10.1152\/ajpheart.00184.2004","article-title":"Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors","volume":"287","author":"B\u00e1tkai","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"key20180919073656_B8","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1096\/fasebj.12.11.1035","article-title":"Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension","volume":"12","author":"Varga","year":"1998","journal-title":"FASEB J."},{"key":"key20180919073656_B9","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1161\/01.HYP.0000174596.95607.fd","article-title":"VR1-mediated depressor effects during high-salt intake: role of anandamide","volume":"46","author":"Wang","year":"2005","journal-title":"Hypertension"},{"key":"key20180919073656_B10","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1096\/fj.06-7460com","article-title":"The transient receptor potential vanilloid 1 (TRPV1) receptor protects against the onset of sepsis after endotoxin","volume":"21","author":"Clark","year":"2007","journal-title":"FASEB J."},{"key":"key20180919073656_B11","doi-asserted-by":"crossref","first-page":"R1517","DOI":"10.1152\/ajpregu.00005.2008","article-title":"TRPV1-mediated protection against endotoxin-induced hypotension and mortality in rats","volume":"294","author":"Wang","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"key20180919073656_B12","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1124\/jpet.106.112904","article-title":"Endocannabinoid regulates blood pressure via activation of the transient receptor potential vanilloid type 1 in Wistar rats fed a high-salt diet","volume":"321","author":"Wang","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"key20180919073656_B13","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1378\/chest.104.1.230","article-title":"A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome","volume":"104","author":"Hebert","year":"1993","journal-title":"Chest"},{"key":"key20180919073656_B14","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1161\/01.HYP.29.5.1204","article-title":"Cardiovascular effects of anandamide in anesthetized and conscious normotensive and hypertensive rats","volume":"29","author":"Lake","year":"1997","journal-title":"Hypertension"},{"key":"key20180919073656_B15","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1161\/01.HYP.28.4.682","article-title":"Mechanism of the hypotensive action of anandamide in anesthetized rats","volume":"28","author":"Varga","year":"1996","journal-title":"Hypertension"},{"key":"key20180919073656_B16","first-page":"526","article-title":"The effects of bacterial endotoxins on host mediation systems. A review","volume":"93","author":"Morrison","year":"1978","journal-title":"Am. J. Pathol."},{"key":"key20180919073656_B17","first-page":"168","article-title":"Hypoxic alterations in cellular signal transduction in shock and sepsis","volume":"4","author":"West","year":"1996","journal-title":"New Horiz."},{"key":"key20180919073656_B18","doi-asserted-by":"crossref","first-page":"F1090","DOI":"10.1152\/ajprenal.00517.2005","article-title":"Pentoxifylline protects against endotoxin-induced acute renal failure in mice","volume":"291","author":"Wang","year":"2006","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"key20180919073656_B19","doi-asserted-by":"crossref","first-page":"F261","DOI":"10.1152\/ajprenal.00263.2006","article-title":"Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipoplysaccharide administration in mice","volume":"292","author":"Wu","year":"2007","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"key20180919073656_B20","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1046\/j.1523-1755.2003.00268.x","article-title":"Ethyl pyruvate decreases sepsis-induced acute renal failure and multiple organ damage in aged mice","volume":"64","author":"Miyaji","year":"2003","journal-title":"Kidney Int."},{"key":"key20180919073656_B21","doi-asserted-by":"crossref","first-page":"F997","DOI":"10.1152\/ajprenal.00130.2004","article-title":"Endotoxemic acute renal failure is attenuated in caspase-1-deficient mice","volume":"288","author":"Wang","year":"2005","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"key20180919073656_B22","doi-asserted-by":"crossref","first-page":"F532","DOI":"10.1152\/ajprenal.00323.2002","article-title":"Interaction among nitric oxide, reactive oxygen species, and antioxidants during endotoxemia-related acute renal failure","volume":"284","author":"Wang","year":"2003","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"key20180919073656_B23","doi-asserted-by":"crossref","first-page":"G1173","DOI":"10.1152\/ajpgi.00420.2006","article-title":"Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic inflammatory response during sepsis","volume":"292","author":"He","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"key20180919073656_B24","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/bja\/aeg034","article-title":"Oxidative stress and gene expression in sepsis","volume":"90","author":"Macdonald","year":"2003","journal-title":"Br. J. Anaesth."},{"key":"key20180919073656_B25","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/BF00856833","article-title":"Neutrophil activation in the hemolytic uremic syndrome: free and complexed elastase in plasma","volume":"6","author":"Fitzpatrick","year":"1992","journal-title":"Pediatr. Nephrol."},{"key":"key20180919073656_B26","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0065-2776(08)60597-0","article-title":"Role of cytokines in sepsis","volume":"66","author":"Hack","year":"1997","journal-title":"Adv. Immunol."},{"key":"key20180919073656_B27","doi-asserted-by":"crossref","first-page":"L1173","DOI":"10.1152\/ajplung.00406.2006","article-title":"Role of transient receptor potential vanilloid 1 receptors in endotoxin-induced airway inflammation in the mouse","volume":"292","author":"Helyes","year":"2007","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"key20180919073656_B28","doi-asserted-by":"crossref","first-page":"5741","DOI":"10.4049\/jimmunol.1102147","article-title":"TRPV1 deletion enhances local inflammation and accelerates the onset of systemic inflammatory response syndrome","volume":"188","author":"Fernandes","year":"2012","journal-title":"J. Immunol."},{"key":"key20180919073656_B29","doi-asserted-by":"crossref","first-page":"H1161","DOI":"10.1152\/ajpheart.1993.264.4.H1161","article-title":"TNF-alpha release in endotoxemia contributes to neutrophil-dependent pulmonary edema","volume":"264","author":"Horgan","year":"1993","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"key20180919073656_B30","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1096\/fasebj.8.8.8181668","article-title":"Adhesion molecules and inflammatory injury","volume":"8","author":"Albelda","year":"1994","journal-title":"FASEB J."},{"key":"key20180919073656_B31","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1172\/JCI407","article-title":"In vivo expression of neutrophil inhibitory factor via gene transfer prevents lipopolysaccharide-induced lung neutrophil infiltration and injury by a beta2 integrin-dependent mechanism","volume":"101","author":"Zhou","year":"1998","journal-title":"J. Clin. Invest."},{"key":"key20180919073656_B32","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/86539","article-title":"Functional alpha4-integrin: a newly identified pathway of neutrophil recruitment in critically ill septic patients","volume":"7","author":"Ibbotson","year":"2001","journal-title":"Nat. Med."},{"key":"key20180919073656_B33","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1124\/jpet.104.078147","article-title":"Mechanisms involved in the enhancement of allergic airways neutrophil influx by permanent C-fiber degeneration in rats","volume":"313","author":"Franco-Penteado","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"key20180919073656_B34","doi-asserted-by":"crossref","first-page":"8323","DOI":"10.1073\/pnas.92.18.8323","article-title":"Specific induction of cAMP in Langerhans cells by calcitonin gene-related peptide: relevance to functional effects","volume":"92","author":"Asahina","year":"1995","journal-title":"Proc. Natl. Acad. 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A."},{"key":"key20180919073656_B35","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1016\/S0196-9781(96)00198-2","article-title":"Enhancement of phagocytosis by calcitonin gene-related peptide (CGRP) in cultured mouse peritoneal macrophages","volume":"17","author":"Ichinose","year":"1996","journal-title":"Peptides"},{"key":"key20180919073656_B36","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1006\/cyto.1999.0607","article-title":"Procalcitonin and calcitonin gene-related peptide decrease LPS-induced TNF production by human circulating blood cells","volume":"12","author":"Monneret","year":"2000","journal-title":"Cytokine"},{"key":"key20180919073656_B37","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1161\/01.HYP.0000168926.44648.ed","article-title":"Role of calcitonin gene-related peptide in hypertension-induced renal damage","volume":"46","author":"Bowers","year":"2005","journal-title":"Hypertension"},{"key":"key20180919073656_B38","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1113\/jphysiol.2005.094292","article-title":"Anandamide elicits an acute release of nitric oxide through endothelial TRPV1 receptor activation in the rat arterial mesenteric bed","volume":"568","author":"Poblete","year":"2005","journal-title":"J. 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