Modulation of acute inflammation by targeting glycosaminoglycan-cytokine interactions.

Abstract

Glycosaminoglycans (GAGs) located on cellular membranes and the extracellular matrix (ECM) are able to interact with chemokines and pro-inflammatory cytokines, leading to local cytokine/chemokine accumulation. The tissue-bound cytokines/chemokines function in promoting leukocyte migration and activation, contributing to local inflammation. Hence, targeting of GAG-cytokine interactions may provide an avenue for the attenuation of inflammatory responses. A cationic peptide (MC2) derived from the heparin-binding sequence of mouse IFN-gamma was previously shown by our laboratory to delay allograft rejection in an animal model. In order to further investigate potential anti-inflammatory properties of the MC2 peptide, we have studied its activity in an acute peritoneal inflammation model. Groups of C57Bl/6 mice were injected intraperitoneally with either ConA or thioglycollate and treated with saline (control), the MC2 peptide or two control cationic peptides, poly-l-lysine (PLL) and poly-l-arginine (PLA). Treatment with the MC2 peptide, but not PLA or PLL, resulted in statistically significant reductions in total cell numbers, concentration of total proteins and concentrations of pro-inflammatory cytokines (TNFalpha, IL-6 or IL-1 beta) in peritoneal lavage fluids, without alterations to the qualitative cellular composition of the exudate. These results suggest that targeting GAG-cytokine interaction is a viable approach to reduce inflammation.

• Authors: James G Cripps, Fabián A Crespo, Peteris Romanovskis, Arno F Spatola, Rafael Fernández-Botrán
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 5 Issue 11 Pg. 1622-32 (Oct 2005) ISSN: 1567-5769 [Print] Netherlands
• PMID: 16039552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Glycosaminoglycans
• MC2 peptide
• MC2 protein, mouse
• Peptide Fragments
• Proteins
• Thioglycolates
• Concanavalin A
• Interferon-gamma

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Apoptosis (drug effects)
• Ascitic Fluid (cytology, metabolism)
• Cells, Cultured
• Concanavalin A
• Cytokines (metabolism, physiology)
• Female
• Glycosaminoglycans (metabolism, physiology)
• Inflammation (chemically induced, drug therapy, metabolism)
• Interferon-gamma (pharmacology)
• Mice
• Mice, Inbred C57BL
• Peptide Fragments (pharmacology)
• Proteins (pharmacology)
• Thioglycolates