PMID- 16039552
OWN - NLM
STAT- MEDLINE
DCOM- 20051213
LR  - 20081121
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 5
IP  - 11
DP  - 2005 Oct
TI  - Modulation of acute inflammation by targeting glycosaminoglycan-cytokine 
      interactions.
PG  - 1622-32
AB  - 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.
FAU - Cripps, James G
AU  - Cripps JG
AD  - Department of Pathology and Laboratory Medicine, School of Medicine, University 
      of Louisville, Louisville, KY 40292, USA.
FAU - Crespo, Fabian A
AU  - Crespo FA
FAU - Romanovskis, Peteris
AU  - Romanovskis P
FAU - Spatola, Arno F
AU  - Spatola AF
FAU - Fernandez-Botran, Rafael
AU  - Fernandez-Botran R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (MC2 peptide)
RN  - 0 (MC2 protein, mouse)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proteins)
RN  - 0 (Thioglycolates)
RN  - 11028-71-0 (Concanavalin A)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Ascitic Fluid/cytology/metabolism
MH  - Cells, Cultured
MH  - Concanavalin A
MH  - Cytokines/metabolism/*physiology
MH  - Female
MH  - Glycosaminoglycans/metabolism/*physiology
MH  - Inflammation/chemically induced/*drug therapy/metabolism
MH  - Interferon-gamma/*pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Peptide Fragments/*pharmacology
MH  - Proteins/*pharmacology
MH  - Thioglycolates
EDAT- 2005/07/26 09:00
MHDA- 2005/12/15 09:00
CRDT- 2005/07/26 09:00
PHST- 2004/09/16 00:00 [received]
PHST- 2005/04/26 00:00 [revised]
PHST- 2005/04/28 00:00 [accepted]
PHST- 2005/07/26 09:00 [pubmed]
PHST- 2005/12/15 09:00 [medline]
PHST- 2005/07/26 09:00 [entrez]
AID - S1567-5769(05)00115-3 [pii]
AID - 10.1016/j.intimp.2005.04.010 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2005 Oct;5(11):1622-32. doi: 10.1016/j.intimp.2005.04.010.