title: IL-21 modulates release of proinflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways.
abstract: The aim of this study was to investigate the anti-inflammatory effect of IL-21 on LPS-induced mouse peritoneal macrophages. The results showed that IL-21 significantly inhibited LPS-induced mRNA expression of IL-1β, TNF-α, and IL-6 in macrophages, but not of IFN-γ, IL-10, CCL5, or CXCL2. ELISA analysis showed that IL-21 also suppressed LPS-induced production of TNF-α and IL-6 in culture supernatants. Western blot analysis showed that IL-21 clearly inhibited ERK and IκBα phosphorylation and NF-κB translocation in LPS-stimulated macrophages, but it increased STAT3 phosphorylation. Flow cytometric and Western blot analysis showed that IL-21 decreased M1 macrophages surface markers expression of CD86, iNOS, and TLR4 in LPS-stimulated cells. All results suggested that IL-21 decreases IL-6 and TNF-α production via inhibiting the phosphorylation of ERK and translocation of NF-κB and promotes a shift from the M1 to M2 macrophage phenotype by decreasing the expression of CD86, iNOS, and TLR4 and by increasing STAT3 phosphorylation in LPS-stimulated cells.
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Su-nan
authors.initials: SN
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Shou-peng
authors.initials: SP
authors.lastname: Fu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China ; College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China.
authors.forename: Jian-fa
authors.initials: JF
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Hong-mei
authors.initials: HM
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Shan-shan
authors.initials: SS
authors.lastname: Xie
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Bing-run
authors.initials: BR
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Qing-kang
authors.initials: QK
authors.lastname: Lv
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Zhi-qiang
authors.initials: ZQ
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Wen-jing
authors.initials: WJ
authors.lastname: Xue
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Bing-xu
authors.initials: BX
authors.lastname: Huang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun 130062, China.
authors.forename: Ju-xiong
authors.initials: JX
authors.lastname: Liu
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D051940:B7-2 Antigen; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D007378:Interleukins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D000098546:Interleukin-21