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Lesion formation was preceded by mast cell trafficking to the lamina propria, and trafficking was mediated by tumor necrosis factor-\u03b1 (TNF). Here, we found that supernatants of TNF-treated urothelial cultures promoted chemotaxis of bone marrow-derived mast cells in vitro that was blocked by anti-RANTES antibodies but unaffected by anti-TNF antibodies. In vivo, PRV infection of wild-type mice induced RANTES expression in the urothelium that was temporally coincident with lamina propria mast cell accumulation (maximum at days 3\u20134 following infection) and was not induced in TNF<jats:sup>\u2212\/\u2212<\/jats:sup>mice, TNFR1\/2<jats:sup>\u2212\/\u2212<\/jats:sup>mice, or mice treated with anti-TNF antibodies. Anti-RANTES antibodies blocked PRV-induced lamina propria mast cell accumulation 56% and reduced the prevalence of animals with detectable lesions 42%, relative to isotype control antibodies. Bladder barrier function was quantified by measuring transepithelial resistance (TER). PRV induced a 49% loss of TER in the presence of control antibodies, but mice treated with anti-RANTES antibodies exhibited reduced TER loss (16%, P &lt; 0.01). These data demonstrate that RANTES plays a key role in the pathogenesis of neurogenic cystitis and suggest that chemokines may represent novel therapeutic targets for IC patients with mast cell-associated disease.<\/jats:p>","DOI":"10.1152\/ajprenal.00472.2006","type":"journal-article","created":{"date-parts":[[2007,1,24]],"date-time":"2007-01-24T03:28:19Z","timestamp":1169609299000},"page":"F1372-F1379","source":"Crossref","is-referenced-by-count":37,"title":["RANTES mediates TNF-dependent lamina propria mast cell accumulation and barrier dysfunction in neurogenic cystitis"],"prefix":"10.1152","volume":"292","author":[{"given":"Michael C.","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavitra","family":"Keshavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg D.","family":"Gregory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Klumpp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.552"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(99)80332-X"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2005.034983"},{"key":"R4","unstructured":"Bamias G, Sugawara K, Pagnini C, Cominelli F.The Th1 immune pathway as a therapeutic target in Crohn's disease.Curr Opin Investig Drugs4: 1279\u20131286, 2003."},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000176633.92150.4e"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2005.07.049"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.1995.tb07840.x"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Buffington CA, Chew DJ, Woodworth BE.Feline interstitial cystitis.J Am Vet Med Assoc215: 682\u2013687, 1999.","DOI":"10.2460\/javma.1999.215.05.682"},{"key":"R9","unstructured":"Card J, Enquist L.Neurovirulence of pseudorabies virus.Crit Rev Neurobiol9: 137\u2013162, 1995."},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)00171-0"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(05)00171-0"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01182.2005"},{"key":"R14","doi-asserted-by":"crossref","unstructured":"Chensue SW, Warmington KS, Allenspach EJ, Lu B, Gerard C, Kunkel SL, Lukacs NW.Differential expression and cross-regulatory function of RANTES during mycobacterial (type 1) and schistosomal (type 2) antigen-elicited granulomatous inflammation.J Immunol163: 165\u2013173, 1999.","DOI":"10.4049\/jimmunol.163.1.165"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1097\/01.ju.0000081163.46167.82"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1159\/000053694"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)62611-9"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)32737-4"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1998.02027.x"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1159\/000013603"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1979.tb01108.x"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)41529-1"},{"key":"R23","unstructured":"Held P, Hanno P, Wein A, Pauly M, Cahn M.Epidemiology of interstitial cystitis. 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