title: In vitro and in vivo downregulation of C3 by lipoteichoic acid isolated from Lactobacillus plantarum K8 suppressed cytokine-mediated complement system activation.
abstract: Complement component 3 (C3) is one of the proteins associated with complement cascades. C3 plays an essential role in three different pathways-the alternative, classical and lectin pathways. It is well known that cytokines activate complement system and increase complement component C3 production. In the current study, we found that lipoteichoic acid isolated from Lactobacillus plantarum K8 (pLTA) inhibited tumor necrosis factor-alpha (TNF-α) or interferon-gamma (IFN-γ)-mediated C3 mRNA and protein expression in HaCaT cells. pLTA inhibited C3 expression through the inhibition of the phosphorylation of p65 and p38 in the TNF-α-treated cells, while the inhibition of STAT1/2 and JAK2 phosphorylation by pLTA contributed to the reduction of C3 in IFN-γ-treated cells. When mice were pre-injected with pLTA followed by re-injection of TNF-α, serum C3 level was decreased as compared to TNF-α-injected only. Further studies revealed that membrane attack complex (MAC) increased by TNF-α injection was lessened in pLTA-pre-injected mice. A bactericidal assay using mouse sera showed that MAC activity in pLTA-pre-injected mice was lower than in TNF-α only-injected mice. These results suggest that pLTA can suppress inflammatory cytokine-mediated complement activation through the inhibition of C3 synthesis. pLTA application has the potential to alleviate complement-mediated diseases caused by excessive inflammation.
authors.affiliation: Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, #308, Life Science Building, Yongin 17104, Republic of Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Jeon
authors.affiliation: Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, #308, Life Science Building, Yongin 17104, Republic of Korea.
authors.forename: Hye Rim
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, #308, Life Science Building, Yongin 17104, Republic of Korea Skin Biotechnology Center, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, Yongin 17104, Republic of Korea.
authors.forename: Hangeun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, #308, Life Science Building, Yongin 17104, Republic of Korea Skin Biotechnology Center, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do, Yongin 17104, Republic of Korea dkchung@khu.ac.kr.
authors.forename: Dae Kyun
authors.initials: DK
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000235:genetics / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D016908:Gram-Positive Bacterial Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D048191:Lactiplantibacillus plantarum / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D013682:Teichoic Acids / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D003176:Complement C3; D015938:Complement Membrane Attack Complex; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C009900:lipoteichoic acid; D007371:Interferon-gamma
keywords: Lactobacillus plantarum; anti-inflammation; complement component C3; cytokine; lipoteichoic acid; membrane attack complex