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.

METHODOLOGY/PRINCIPAL FINDINGS:

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/SIGNIFICANCE:

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: Xiaolu Yang, Huiyi Jin, Kun Liu, Qing Gu, Xun Xu
• Journal: PloS one (PLoS One) Vol. 6 Issue 12 Pg. e29155 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 22195011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antigens, Neoplasm
• Biomarkers, Tumor
• Chemokine CCL2
• Interleukin-6
• Lectins, C-Type
• Lipopolysaccharides
• NF-kappa B
• Pancreatitis-Associated Proteins
• Peptides
• REG3A protein, human
• Reg3b protein, rat
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1

Topics

• Amino Acid Sequence
• Animals
• Anti-Inflammatory Agents (administration & dosage, chemistry, pharmacology, therapeutic use)
• Antigens, Neoplasm (chemistry)
• Aqueous Humor (drug effects, metabolism)
• Biomarkers, Tumor (chemistry)
• Chemokine CCL2 (metabolism)
• Gene Expression Regulation (drug effects)
• Human Umbilical Vein Endothelial Cells (drug effects, metabolism)
• Humans
• Inflammation (complications, drug therapy, pathology)
• Intercellular Adhesion Molecule-1 (metabolism)
• Interleukin-6 (genetics, metabolism)
• Intravitreal Injections
• Lectins, C-Type (chemistry)
• Lipopolysaccharides
• Mice
• Molecular Sequence Data
• NF-kappa B (metabolism)
• Pancreatitis-Associated Proteins
• Peptides (administration & dosage, chemistry, pharmacology, therapeutic use)
• Phosphorylation (drug effects)
• Protein Structure, Tertiary
• Protein Transport (drug effects)
• Rats
• Retina (drug effects, metabolism, pathology)
• Signal Transduction (drug effects)
• Tumor Necrosis Factor-alpha (genetics, metabolism, pharmacology)
• Uveitis (chemically induced, complications, drug therapy, pathology)