Palmitic acid induces interleukin-1β secretion via NLRP3 inflammasomes and inflammatory responses through ROS production in human placental cells.
Maternal obesity, a major risk factor for adverse pregnancy complications, results in inflammatory cytokine release in the placenta. Levels of free fatty acids are elevated in the plasma of obese human. These fatty acids include obesity-related palmitic acids, which is a major saturated fatty acid, that promotes inflammatory responses. Increasing evidence indicates that nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3) inflammasomes mediate inflammatory responses induced by endogenous danger signals. We hypothesized that inflammatory responses associated with gestational obesity cause inflammation. To test this hypothesis, we investigated the effect of palmitic acid on the activation of NLRP3 inflammasomes and inflammatory responses in a human Sw.71 trophoblast cell line. Palmitic acid stimulated caspase-1 activation and markedly increased interleukin (IL)-1β secretion in Sw.71 cells. Treatment with a caspase-1 inhibitor diminished palmitic acid-induced IL-1β release. In addition, NLRP3 and caspase-1 genome editing using a CRISPR/Cas9 system in Sw.71 cells suppressed IL-1β secretion, which was stimulated by palmitic acid. Moreover, palmitic acid stimulated caspase-3 activation and inflammatory cytokine secretion (e.g., IL-6 and IL-8). Palmitic acid-induced cytokine secretion were dependent on caspase-3 activation. In addition, palmitic acid-induced IL-1β, IL-6, and IL-8 secretion was depended on reactive oxygen species (ROS) generation. In conclusion, palmitic acid caused activation of NLRP3 inflammasomes and inflammatory responses, inducing IL-1β, IL-6, and IL-8 secretion, which is associated with ROS generation, in human Sw.71 placental cells. We suggest that obesity-related palmitic acid induces placental inflammation, resulting in association with pregnancy complications.
Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034, Japan. Electronic address: ks205312@nodai.ac.jp.
Koumei
K
Shirasuna
Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034, Japan.
Hiroki
H
Takano
Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034, Japan.
Kotomi
K
Seno
Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034, Japan.
Ayaka
A
Ohtsu
Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
Tadayoshi
T
Karasawa
Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
Masafumi
M
Takahashi
Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
Akihide
A
Ohkuchi
Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
Hirotada
H
Suzuki
Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
Shigeki
S
Matsubara
Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034, Japan.
Hisataka
H
Iwata
Laboratory of Animal Reproduction, Department of Agriculture, Tokyo University of Agriculture, Atsugi, Kanagawa 243-0034, Japan.
Takehito
T
Kuwayama
D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D009765:Obesity / Q000276:immunology*; D019308:Palmitic Acid / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology
D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D020170:Caspase 1
Inflammasome; Obesity; Palmitic acid; Placenta; Reactive oxygen species