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.
Highlights
Surfactant protein D (SP-D), a member of C-type lectin family, plays an important role in host defense and regulating inflammation during infections[9]
When pathogenic microbes invade, carbohydrate recognition domain (CRD) binds to microbial carbohydrates, the collagenous tail interacts with CD91 of inflammatory cells to stimulate Nuclear factor-kappa B (NF-κ B) activation, which induces the production of inflammatory cytokines[18,19]
Using the cecal ligation and puncture (CLP) sepsis model to cause acute pancreatic injury (API) in surfactant protein D (SP-D) KO and wild type (WT) mice we found that SP-D play a protective role in the sepsis-induced API by modulating NF-κ B-mediated inflammation and inhibiting apoptosis
Summary
Surfactant protein D (SP-D), a member of C-type lectin family, plays an important role in host defense and regulating inflammation during infections[9]. When pathogenic microbes invade, CRD binds to microbial carbohydrates, the collagenous tail interacts with CD91 of inflammatory cells to stimulate NF-κ B activation, which induces the production of inflammatory cytokines[18,19]. For these reasons, we hypothesized that SP-D has a role in the pathogenesis of sepsis-induced acute pancreatic injury (API). SP-D-mediated immune responses have been studied using various pathogenic organisms in SP-D-null mice These provide evidence that SP-D has a protective function in various infections, because the SP-D knockout (KO) mice show higher susceptibility to bacterial and viral pathogens[20,21]. Using the cecal ligation and puncture (CLP) sepsis model to cause API in SP-D KO and wild type (WT) mice we found that SP-D play a protective role in the sepsis-induced API by modulating NF-κ B-mediated inflammation and inhibiting apoptosis
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