{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:37:17Z","timestamp":1790854637735,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,2,22]],"date-time":"2011-02-22T00:00:00Z","timestamp":1298332800000},"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":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypertrophic scar (HTS), a fibroproliferative disorder (FPD), complicates burn wound healing. Although the pathogenesis is not understood, prolonged inflammation is a known contributing factor. Emerging evidence suggests that fibroblasts regulate immune\/inflammatory responses through toll\u2010like receptor 4 (TLR4) activated by lipopolysaccharide (LPS) through adaptor molecules, leading to nuclear factor kappa\u2010light\u2010chain\u2010enhancer of activated B cells and mitogen\u2010activated protein kinases activation, cytokine gene transcription and co\u2010stimulatory molecule expression resulting in inflammation. This study explored the possible role of TLR4 in HTS formation. Paired normal and HTS tissue from burn patients was collected and dermal fibroblasts isolated and cultured. Immunohistochemical analysis of tissues demonstrated increased TLR4 staining in HTS tissue. Quantitative RT\u2010PCR of three pairs of fibroblasts demonstrated mRNA levels for TLR4 and its legend myeloid differentiation factor 88 (MyD88) in HTS fibroblasts were increased significantly compared with normal fibroblasts. Flow cytometry showed increased TLR4 expression in HTS fibroblasts compared with normal. ELISA demonstrated protein levels for prostaglandin E2, interleukin (IL)\u20106, IL\u20108 and monocyte chemotactic protein\u20101 (MCP\u20101) were significantly increased in HTS fibroblasts compared to normal. When paired normal and HTS fibroblasts were stimulated with LPS, significant increases in mRNA and protein levels for MyD88, IL\u20106, IL\u20108, and MCP\u20101 were detected. However, when transfected with MyD88 small interfering RNA (siRNA), then stimulated with LPS, a significant decrease in mRNA and protein levels for these molecules compared to only LPS\u2010stimulated fibroblasts was detected. In comparison, a scramble siRNA transfection did not affect mRNA or protein levels for these molecules. Results demonstrate LPS stimulates proinflammatory cytokine expression in dermal fibroblasts and MyD88 siRNA eliminates the expression. Therefore, controlling inflammation and manipulating TLR signaling in skin cells may result in novel treatment strategies for HTS and other FPD. J. Cell. Physiol. 226: 1265\u20131273, 2011. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.22454","type":"journal-article","created":{"date-parts":[[2010,10,13]],"date-time":"2010-10-13T14:19:31Z","timestamp":1286979571000},"page":"1265-1273","source":"Crossref","is-referenced-by-count":127,"title":["Toll\u2010like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring"],"prefix":"10.1002","volume":"226","author":[{"given":"JianFei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keijiro","family":"Hori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Ladak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward E.","family":"Tredget","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,2,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-32636-7_1"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ta.0000240175.18189.af"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1737"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0952-7915(99)00046-1"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59430-4_7"},{"key":"e_1_2_6_8_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1097\/SHK.0b013e3181454975","article-title":"Toll\u2010like receptor 4 contributes to microvascular inflammation and barrier dysfunction in thermal injury","volume":"29","author":"Breslin JW","year":"2008","journal-title":"Shock"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200003)30:3<914::AID-IMMU914>3.0.CO;2-D"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(01)01863-4"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2004.03.009"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(98)00106-9"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2006.11.005"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005373-198310000-00009"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.21497"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35078107"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700302"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780371116"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00929499"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.30.17779"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(200108)194:4<393::AID-PATH907>3.0.CO;2-7"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1996.d01-759.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.2000.1631"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/35006097"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5441.950"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.2741\/2955"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04651.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00793.2005"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.01021.x"},{"key":"e_1_2_6_30_1","first-page":"711","article-title":"Production of monocyte chemoattractant protein\u20101 and macrophage inflammatory protein\u20101 alpha by inflammatory granuloma fibroblasts","volume":"144","author":"Lukacs NW","year":"1994","journal-title":"Am J Pathol"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1204698"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2007.06.014"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-007-0061-8"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708601112"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.shk.0000228797.41044.08"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.5.2957"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.2307\/3580049"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1193"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24140"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2005.11.021"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119178"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.6.1873"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4160-3274-8.50050-7"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1663"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-3083.2001.00846.x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.138.12.5576"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.1.295-301.1991"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6093"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.11.4932-4937.1992"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb07955.x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2006.26.179"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1067-1927.2004.012113.x"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0507306"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2007.00261.x"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2006.00192.x"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2007.0104"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.101"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.164"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(2001010)31:10<2936::AID-IMMU2936>3.0.CO;2-0"},{"key":"e_1_2_6_60_1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.4049\/jimmunol.160.3.1053","article-title":"CD40 engagement up\u2010regulates cyclooxygenase\u20102 expression and prostaglandin E2 production in human lung fibroblasts","volume":"160","author":"Zhang Y","year":"1998","journal-title":"J Immunol"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0195-8"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.22454","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.22454","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T20:48:27Z","timestamp":1697489307000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.22454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,2,22]]},"references-count":60,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["10.1002\/jcp.22454"],"URL":"https:\/\/doi.org\/10.1002\/jcp.22454","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,2,22]]}}}