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To assess whether AAGs also induce host\u2010directed immunomodulatory responses, we determined the AAG\u2010dependent induction of cytokines in macrophages in the absence or presence of lipopolysaccharide (LPS). Our results show for the first time that AAGs can boost the innate immune response, specifically the recruitment of immune cells such as neutrophils required for the resolution of infections. Moreover, AAGs can selectively control inflammatory responses induced in the presence of endotoxins to prevent septic shock. In conclusion, our study demonstrates that AAGs possess multifunctional properties that combine direct antibacterial activity with host\u2010directed clearance effects reminiscent of those of host\u2010defense peptides.<\/jats:p>","DOI":"10.1002\/anie.201500598","type":"journal-article","created":{"date-parts":[[2015,4,2]],"date-time":"2015-04-02T21:14:57Z","timestamp":1428009297000},"page":"6278-6282","source":"Crossref","is-referenced-by-count":56,"title":["Amphiphilic Tobramycins with Immunomodulatory Properties"],"prefix":"10.1002","volume":"54","author":[{"given":"Goutam","family":"Guchhait","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Altieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balakishan","family":"Gorityala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Findlay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.","family":"Zhanel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeloffer","family":"Mookherjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Schweizer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4]]},"reference":[{"key":"e_1_2_2_1_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2013.86"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399410001766"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.06.008"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm800345u"},{"key":"e_1_2_2_6_2","first-page":"51","author":"Zhang J.","journal-title":"J."},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm900615h"},{"key":"e_1_2_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm1000437"},{"key":"e_1_2_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2011.01.014"},{"key":"e_1_2_2_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm401148j"},{"key":"e_1_2_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02536-13"},{"key":"e_1_2_2_12_2","unstructured":"\u00a0"},{"key":"e_1_2_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200761"},{"key":"e_1_2_2_13_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201200761"},{"key":"e_1_2_2_14_2","doi-asserted-by":"publisher","DOI":"10.1039\/C2MD20162C"},{"key":"e_1_2_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2009.66"},{"key":"e_1_2_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.01.073"},{"key":"e_1_2_2_17_2","unstructured":"\u00a0"},{"key":"e_1_2_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/183618a0"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.274"},{"key":"e_1_2_2_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja056159z"},{"key":"e_1_2_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb3005116"},{"key":"e_1_2_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.07.004"},{"key":"e_1_2_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1393"},{"key":"e_1_2_2_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja303304j"},{"key":"e_1_2_2_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052449"},{"key":"e_1_2_2_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17545"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.525"},{"key":"e_1_2_2_28_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2012.656090"},{"key":"e_1_2_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(02)01624-1"},{"key":"e_1_2_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(02)00153-9"},{"key":"e_1_2_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12018"},{"key":"e_1_2_2_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2455"},{"key":"e_1_2_2_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12291"},{"key":"e_1_2_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.5.1727-1732.2005"},{"key":"e_1_2_2_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.7.3883"},{"key":"e_1_2_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1994.tb44245.x"},{"key":"e_1_2_2_37_2","first-page":"391","volume":"72","author":"Mukaida N.","year":"2000","journal-title":"Int. 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