{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:23:29Z","timestamp":1790198609165,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,11,23]],"date-time":"2012-11-23T00:00:00Z","timestamp":1353628800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inflammatory bowel disease (IBD) patients display elevated levels of intraluminal nitric oxide (NO). NO can react with other molecules to form toxic compounds, which has led to the idea that NO may be an important mediator of IBD. However, the cellular source of NO and how its production is regulated in the intestine are unclear. In this study we aimed to determine if intestinal myofibroblasts produce NO in response to the IBD\u2010associated cytokines IL\u20101\u03b2, TNF\u03b1, and IFN\u03b3. Intestinal myofibroblasts were isolated from mice and found to express inducible nitric oxide synthase (iNOS) mRNA, but not endothelial NOS or neuronal NOS. Individual treatment of myofibroblasts with IL\u20101\u03b2, TNF\u03b1, or IFN\u03b3 had no effect on NO production, but stimulation with combinations of these cytokines synergistically increased iNOS mRNA and protein expression. Treatment with TNF\u03b1 or IFN\u03b3 increased cell surface expression of IFN\u03b3RI or TNFRII, respectively, suggesting that these cytokines act in concert to prime NO production by myofibroblasts. Impairment of NF\u2010\u03baB activity with a small molecule inhibitor was sufficient to prevent increased expression of IFN\u03b3RI or TNFRII, and inhibition of Akt, JAK\/STAT, or NF\u2010\u03baB blocked nearly all NO production induced by combinatorial cytokine treatment. These data indicate that intestinal myofibroblasts require stimulation by multiple cytokines to produce NO and that these cytokines act through a novel pathway involving reciprocal cytokine receptor regulation and signaling by Akt, JAK\/STAT, and NF\u2010\u03baB. J. Cell. Physiol. 228: 572\u2013580, 2013. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcp.24164","type":"journal-article","created":{"date-parts":[[2012,7,25]],"date-time":"2012-07-25T12:12:44Z","timestamp":1343218364000},"page":"572-580","source":"Crossref","is-referenced-by-count":11,"title":["Intestinal myofibroblasts produce nitric oxide in response to combinatorial cytokine stimulation"],"prefix":"10.1002","volume":"228","author":[{"given":"Jianfeng","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taned","family":"Chitapanarux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Russell K.","family":"Soon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Hal F.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1996.270.2.G225"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1385\/IR:23:2-3:157"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00309.2003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1995.1086"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91476-3"},{"key":"e_1_2_6_7_1","first-page":"G418","article-title":"Nitric oxide generators and cGMP stimulate mucus secretion by rat gastric mucosal cells","volume":"265","author":"Brown JF","year":"1993","journal-title":"Am J Physiol"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2008.04.025"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00325.2003"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520252903099"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200320335"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00413.2004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(87)90841-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj2980249"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-010-0245-1"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.46.373"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1995.tb15938.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.43.1.56"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2004.01984.x"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v12.i21.3386"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)90460-X"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00048.2001"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63931-4"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)90211-X"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0022-3565(25)10238-3","article-title":"Amelioration of chronic ileitis by nitric oxide synthase inhibition","volume":"264","author":"Miller MJ","year":"1993","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1994.tb06048.x"},{"key":"e_1_2_6_27_1","first-page":"1237","article-title":"Multiple redox regulation in NF\u2010kappaB transcription factor activation","volume":"378","author":"Piette J","year":"1997","journal-title":"Biol Chem"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1999.277.2.C183"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"G653","DOI":"10.1152\/ajpgi.2000.279.4.G653","article-title":"Fibrogenesis. 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