title: Innate Immune Molecule Surfactant Protein D Attenuates Sepsis-induced Acute Pancreatic Injury through Modulating Apoptosis and NF-κB-mediated Inflammation.
abstract: Sepsis causes multiple-organ dysfunction including pancreatic injury, thus resulting in high mortality. Innate immune molecule surfactant protein D (SP-D) plays a critical role in host defense and regulating inflammation of infectious diseases. In this study we investigated SP-D functions in the acute pancreatic injury (API) with C57BL/6 Wild-type (WT) and SP-D knockout (KO) mice in cecal ligation and puncture (CLP) model. Our results confirm SP-D expression in pancreatic islets and intercalated ducts and are the first to explore the role of pancreatic SP-D in sepsis. CLP decreased pancreatic SP-D levels and caused severe pancreatic injury with higher serum amylase 24 h after CLP. Apoptosis and neutrophil infiltration were increased in the pancreas of septic KO mice (p < 0.05, vs septic WT mice), with lower Bcl-2 and higher caspase-3 levels in septic KO mice (p < 0.05). Molecular analysis revealed increased NF-κB-p65 and phosphorylated IκB-α levels along with higher serum levels of TNF-α and IL-6 in septic KO mice compared to septic WT mice (p < 0.01). Furthermore, in vitro islet cultures stimulated with LPS produced higher TNF-α and IL-6 (p < 0.05) from KO mice compared to WT mice. Collectively, these results demonstrate SP-D plays protective roles by inhibiting apoptosis and modulating NF-κB-mediated inflammation in CLP-induced API.
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.|Department of Surgery, Wuhan University, Renmin Hospital, Wuhan 430060, Hubei Province, P.R.C.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Jiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Osama
authors.initials: O
authors.lastname: Abdel-Razek
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Yongan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Cooney
authors.affiliation: Department of Surgery, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
authors.forename: Guirong
authors.initials: G
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis; D008026:Ligation; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics; D010179:Pancreas / Q000276:immunology / Q000293:injuries / Q000378:metabolism*; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis / Q000235:genetics*; D011677:Punctures; D018805:Sepsis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D037663:Pulmonary Surfactant-Associated Protein D; D014409:Tumor Necrosis Factor-alpha