TY - JOUR
T1 - Synthetic Cationic Peptide IDR-1018 Modulates Human Macrophage Differentiation
AU - Pena, Olga M.
AU - Afacan, Nicole
AU - Pistolic, Jelena
AU - Chen, Carol
AU - Madera, Laurence
AU - Falsafi, Reza
AU - Fjell, Christopher D.
AU - Hancock, Robert E.W.
N1 - Funding Information:
We would like to thank Danay Maestre-Batlle, who help with some of the technical work. O.M.P. is the recipient of a Canadian Institutes for Health Research Vanier Canada Graduate scholarship; N.J.A is a holder of a Natural Sciences and Engineering Research Council Canada Graduate Studentship and R.E.W.H. is a Canada Research Chair in Genomics and Health.
PY - 2013/1/7
Y1 - 2013/1/7
N2 - Macrophages play a critical role in the innate immune response. To respond in a rapid and efficient manner to challenges in the micro-environment, macrophages are able to differentiate towards classically (M1) or alternatively (M2) activated phenotypes. Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defence peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on innate immune cells like monocytes/macrophages. Here we tested the effect of IDR-1018 on macrophage differentiation, a process essential to macrophage function and the immune response. Using transcriptional, protein and systems biology analysis, we observed that differentiation in the presence of IDR-1018 induced a unique signature of immune responses including the production of specific pro and anti-inflammatory mediators, expression of wound healing associated genes, and increased phagocytosis of apoptotic cells. Transcription factor IRF4 appeared to play an important role in promoting this IDR-1018-induced phenotype. The data suggests that IDR-1018 drives macrophage differentiation towards an intermediate M1-M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection. Synthetic peptides like IDR-1018, which act by modulating the immune system, could represent a powerful new class of therapeutics capable of treating the rising number of multidrug resistant infections as well as disorders associated with dysregulated immune responses.
AB - Macrophages play a critical role in the innate immune response. To respond in a rapid and efficient manner to challenges in the micro-environment, macrophages are able to differentiate towards classically (M1) or alternatively (M2) activated phenotypes. Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defence peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on innate immune cells like monocytes/macrophages. Here we tested the effect of IDR-1018 on macrophage differentiation, a process essential to macrophage function and the immune response. Using transcriptional, protein and systems biology analysis, we observed that differentiation in the presence of IDR-1018 induced a unique signature of immune responses including the production of specific pro and anti-inflammatory mediators, expression of wound healing associated genes, and increased phagocytosis of apoptotic cells. Transcription factor IRF4 appeared to play an important role in promoting this IDR-1018-induced phenotype. The data suggests that IDR-1018 drives macrophage differentiation towards an intermediate M1-M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection. Synthetic peptides like IDR-1018, which act by modulating the immune system, could represent a powerful new class of therapeutics capable of treating the rising number of multidrug resistant infections as well as disorders associated with dysregulated immune responses.
UR - http://www.scopus.com/inward/record.url?scp=84872028125&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0052449
DO - 10.1371/journal.pone.0052449
M3 - Article
C2 - 23308112
AN - SCOPUS:84872028125
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 1
M1 - e52449
ER -