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Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in preterm infants.

Chan KY, Leung FW, Lam HS, Tam YH, To KF, Cheung HM, Leung KT, Poon TC, Lee KH, Li K, Fok TF, Ng PC - PLoS ONE (2012)

Bottom Line: In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF).The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation.Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.

ABSTRACT
Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients.

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Differentially expressed immunoregulatory proteins in NEC and SIP infants.The plasma profiles of 174 immunoregulatory proteins in infants with NEC (n = 5) and SIP (n = 4) were compared with those in gestational age-matched control infants (n = 5; CTL), using the human Cytokine Antibody Array assay. Using a 2-fold change as the cut- off criterion, differentially up-regulated [Figure 1A] and down-regulated [Figure 1B] proteins in NEC and SIP relative to CTL infants were listed under functional categories.
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pone-0036977-g001: Differentially expressed immunoregulatory proteins in NEC and SIP infants.The plasma profiles of 174 immunoregulatory proteins in infants with NEC (n = 5) and SIP (n = 4) were compared with those in gestational age-matched control infants (n = 5; CTL), using the human Cytokine Antibody Array assay. Using a 2-fold change as the cut- off criterion, differentially up-regulated [Figure 1A] and down-regulated [Figure 1B] proteins in NEC and SIP relative to CTL infants were listed under functional categories.

Mentions: Using a 2-fold change as the threshold (Table S1), 26 proteins were up-regulated in NEC infants and 17 proteins in SIP infants, compared with controls (Figure 1A). In addition, 7 and 6 proteins were down-regulated in NEC and SIP infants, respectively (Figure 1B). These proteins could be classified into different functional groups of pro-inflammation (14 proteins), anti-inflammation (8 proteins), cell growth (6 proteins), angiogenesis (5 proteins), wound healing (3 proteins), anti-apoptosis (1 protein), cell adhesion (1 protein), extracellular matrix reorganization (1 protein) and neuropeptide (1 protein). Importantly, some dysregulated proteins were common to NEC and SIP, whereas others were more specific to individual diseases (Figure 1). The disparity of clinical manifestations between NEC and SIP could be further reflected in their protein profiles (Figure 1).


Immunoregulatory protein profiles of necrotizing enterocolitis versus spontaneous intestinal perforation in preterm infants.

Chan KY, Leung FW, Lam HS, Tam YH, To KF, Cheung HM, Leung KT, Poon TC, Lee KH, Li K, Fok TF, Ng PC - PLoS ONE (2012)

Differentially expressed immunoregulatory proteins in NEC and SIP infants.The plasma profiles of 174 immunoregulatory proteins in infants with NEC (n = 5) and SIP (n = 4) were compared with those in gestational age-matched control infants (n = 5; CTL), using the human Cytokine Antibody Array assay. Using a 2-fold change as the cut- off criterion, differentially up-regulated [Figure 1A] and down-regulated [Figure 1B] proteins in NEC and SIP relative to CTL infants were listed under functional categories.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351425&req=5

pone-0036977-g001: Differentially expressed immunoregulatory proteins in NEC and SIP infants.The plasma profiles of 174 immunoregulatory proteins in infants with NEC (n = 5) and SIP (n = 4) were compared with those in gestational age-matched control infants (n = 5; CTL), using the human Cytokine Antibody Array assay. Using a 2-fold change as the cut- off criterion, differentially up-regulated [Figure 1A] and down-regulated [Figure 1B] proteins in NEC and SIP relative to CTL infants were listed under functional categories.
Mentions: Using a 2-fold change as the threshold (Table S1), 26 proteins were up-regulated in NEC infants and 17 proteins in SIP infants, compared with controls (Figure 1A). In addition, 7 and 6 proteins were down-regulated in NEC and SIP infants, respectively (Figure 1B). These proteins could be classified into different functional groups of pro-inflammation (14 proteins), anti-inflammation (8 proteins), cell growth (6 proteins), angiogenesis (5 proteins), wound healing (3 proteins), anti-apoptosis (1 protein), cell adhesion (1 protein), extracellular matrix reorganization (1 protein) and neuropeptide (1 protein). Importantly, some dysregulated proteins were common to NEC and SIP, whereas others were more specific to individual diseases (Figure 1). The disparity of clinical manifestations between NEC and SIP could be further reflected in their protein profiles (Figure 1).

Bottom Line: In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF).The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation.Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.

ABSTRACT
Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are the most common acute surgical emergencies associated with high morbidity and mortality in preterm infants. We aimed to compare the profiles of immunoregulatory proteins and identify novel mediators in plasma of NEC and SIP infants. We also investigated the expression of target genes in resected intestinal tissues and an enterocyte cell line. Using Cytokine Antibody Array assay, we reported the first comparative profiles of immunoregulatory proteins in plasma of NEC and SIP infants, and showed that dysregulated proteins belonged to functionally diversified categories, including pro- and anti-inflammation, angiogenesis, cell growth, wound healing, anti-apoptosis, cell adhesion and extracellular matrix reorganization. Validation by ELISA confirmed significantly higher concentrations of interleukin (IL)-6, angiopoietin (Ang)-2, soluble type II interleukin-1 receptor (sIL-1RII), and soluble urokinase-type plasminogen activator receptor (suPAR) in NEC infants compared with gestational age-matched control, and a lower level of an epidermal growth factor receptor, secreted form of receptor tyrosine-protein kinase ErbB3 (sErbB3), compared with SIP infants. mRNA expressions of IL1-RII and uPAR were up-regulated in resected bowel tissues from NEC infants, indicating that immunoregulation also occurred at the cellular level. In FHs-74 Int cells, Ang-2, IL1-RII and uPAR mRNA expressions were significantly induced by the combined treatment with lipopolysaccharide (LPS) and platelet activating factor (PAF). Our study provided plasmatic signatures of immunoregulatory proteins in NEC and SIP infants, and demonstrated involvement of multiple functional pathways. The magnitude of changes in these proteins was significantly more extensive in NEC infants, reflecting the different nature of injury and/or severity of inflammation. We speculate that dysregulation of IL-6, Ang-2, IL-1RII and uPAR occurred at both systemic and cellular levels, and probably mediated via LPS and endogeneous PAF signals. Such exaggerated immunologic responses may account for the high morbidity and mortality in NEC compared with SIP patients.

Show MeSH
Related in: MedlinePlus