TY - JOUR
T1 - The anti-inflammatory effect of the gut lactic acid bacteria-generated metabolite 10-oxo-cis-6,trans-11-octadecadienoic acid on monocytes
AU - Hagiwara, Shuhei
AU - Nagata, Kazuki
AU - Kasakura, Kazumi
AU - Sakata, Fumiya
AU - Kishino, Shigenobu
AU - Ogawa, Jun
AU - Yashiro, Takuya
AU - Nishiyama, Chiharu
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/9/10
Y1 - 2020/9/10
N2 - We evaluated the effect of gut bacterial metabolites of polyunsaturated fatty acids on inflammation and found that 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC) strikingly suppressed LPS-induced IL-6 release from bone marrow-derived macrophages (BMMs), which was accompanied by reduced mRNA expression of Il6, TNF, and Il1b. γKetoC decreased the cAMP concentration in BMMs, suggesting that γKetoC stimulated G protein-coupled receptors. A Gq agonist significantly suppressed LPS-induced IL-6 expression in BMMs, whereas a Gi inhibitor partially abrogated γKetoC-mediated IL-6 suppression. Cytosolic Ca2+ was markedly increased by γKetoC, which was partly but not fully abrogated by an ion channel inhibitor. Taken together, these data suggest that γKetoC suppresses inflammatory cytokine expression in macrophages primarily through Gq and partially through Gi. γKetoC suppressed osteoclast development and IL-6 expression in synovial fibroblasts from rheumatoid arthritis (RA) patients, suggesting the beneficial effect of γKetoC on the prevention or treatment of RA.
AB - We evaluated the effect of gut bacterial metabolites of polyunsaturated fatty acids on inflammation and found that 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC) strikingly suppressed LPS-induced IL-6 release from bone marrow-derived macrophages (BMMs), which was accompanied by reduced mRNA expression of Il6, TNF, and Il1b. γKetoC decreased the cAMP concentration in BMMs, suggesting that γKetoC stimulated G protein-coupled receptors. A Gq agonist significantly suppressed LPS-induced IL-6 expression in BMMs, whereas a Gi inhibitor partially abrogated γKetoC-mediated IL-6 suppression. Cytosolic Ca2+ was markedly increased by γKetoC, which was partly but not fully abrogated by an ion channel inhibitor. Taken together, these data suggest that γKetoC suppresses inflammatory cytokine expression in macrophages primarily through Gq and partially through Gi. γKetoC suppressed osteoclast development and IL-6 expression in synovial fibroblasts from rheumatoid arthritis (RA) patients, suggesting the beneficial effect of γKetoC on the prevention or treatment of RA.
KW - Inflammation
KW - Molecular biology
KW - Monocyte/macrophages
KW - γKetoC
UR - http://www.scopus.com/inward/record.url?scp=85089188451&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2020.07.006
DO - 10.1016/j.bbrc.2020.07.006
M3 - Article
C2 - 32828309
AN - SCOPUS:85089188451
SN - 0006-291X
VL - 530
SP - 342
EP - 347
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -