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2014 ; 111
(6
): 1210-21
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Lentivirus delivery of IL-10 to promote and sustain macrophage polarization
towards an anti-inflammatory phenotype
#MMPMID24375008
Boehler RM
; Kuo R
; Shin S
; Goodman AG
; Pilecki MA
; Gower RM
; Leonard JN
; Shea LD
Biotechnol Bioeng
2014[Jun]; 111
(6
): 1210-21
PMID24375008
show ga
Gene delivery from biomaterials can create an environment that promotes and
guides tissue formation. However, the immune response induced upon biomaterial
implantation can be detrimental to tissue regeneration. Macrophages play a
central role in mediating early phases of this response, and functional
"polarization" of macrophages towards M1 (inflammatory) or M2 (anti-inflammatory)
phenotypes may bias the local immune state at the implant site. Since gene
delivery from biomaterial scaffolds can confer transgene expression in
macrophages in vivo, we investigated whether transduction of macrophages with an
IL-10 encoding lentivirus can (1) induce macrophage polarization toward an M2
phenotype even in an pro-inflammatory environment, and (2) prevent a shift in
polarization from M2 to M1 following exposure to pro-inflammatory stimuli. IL-10
lentivirus delivery to pre-polarized M1 macrophages reduced TNF-? production
1.5-fold when compared to cells treated with either a control virus or a bolus
delivery of recombinant IL-10 protein. IL-10 lentivirus delivery to naïve
macrophages reduced the amount of TNF-? produced following an inflammatory
challenge by 2.5-fold compared to cells treated with both the control virus and
recombinant IL-10. At a mechanistic level, IL-10 lentivirus delivery mediated
sustained reduction in NF-?B activation and, accordingly, reduced transcription
of TNF-?. In sum, lentiviral delivery of IL-10 to macrophages represents a
promising strategy for directing and sustaining macrophage polarization towards
an M2 phenotype in order to promote local immune responses that facilitate tissue
engineering.