title: A novel peptide derived from human pancreatitis-associated protein inhibits inflammation in vivo and in vitro and blocks NF-kappa B signaling pathway.
abstract: BACKGROUND
  Pancreatitis-associated protein (PAP) is a pancreatic secretory protein belongs to the group VII of C-type lectin family. Emerging evidence suggests that PAP plays a protective effect in inflammatory diseases. In the present study, we newly identified a 16-amino-acid peptide (named PAPep) derived from C-type lectin-like domain (CTLD) of human PAP with potent anti-inflammatory activity using both in vivo and in vitro assays.
  
  
  RESULTS
  We assessed the anti-inflammatory effect of PAPep on endotoxin-induced uveitis (EIU) in rats and demonstrated that intravitreal pretreatment of PAPep concentration-dependently attenuated clinical manifestation of EIU rats, reduced protein leakage and cell infiltration into the aqueous humor (AqH), suppressed tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein (MCP)-1 production in ocular tissues, and improved histopathologic manifestation of EIU. Furthermore, PAPep suppressed the LPS-induced mRNA expression of TNF-α and IL-6 in RAW 264.7 cells, inhibited protein expression of ICAM-1 in TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) as well as U937 cells adhesion to HUVECs. Western blot analysis in ocular tissues and different cell lines revealed that the possible mechanism for this anti-inflammatory effect of PAPep may depend on its ability to inhibit the activation of NF-kB signaling pathway.
  
  
  CONCLUSIONS
  Our studies provide the first evidence that the sequence of PAPep is within the critically active region for the anti-inflammatory function of PAP and the peptide may be a promising candidate for the management of ocular inflammatory diseases.
authors.affiliation: Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yang
authors.forename: Huiyi
authors.initials: H
authors.lastname: Jin
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Gu
authors.forename: Xun
authors.initials: X
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000737:chemistry*; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000737:chemistry*; D018932:Chemokine CCL2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D058449:Intravitreal Injections; D037181:Lectins, C-Type / Q000737:chemistry*; D008070:Lipopolysaccharides; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D000073718:Pancreatitis-Associated Proteins; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014605:Uveitis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D018932:Chemokine CCL2; D015850:Interleukin-6; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000073718:Pancreatitis-Associated Proteins; D010455:Peptides; C000612141:REG3A protein, human; C000612144:Reg3b protein, rat; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1