Gamma-Linolenic Acid Suppresses NF-κΒ Signaling via CD36 in the Lipopolysaccharide-Induced Inflammatory Response in Primary Goat Mammary Gland Epithelial Cells.
Gamma-linolenic acid (GLA) and linoleic acid (LA), which are both n-6 unsaturated fatty acids, play vital roles in lipopolysaccharide (LPS)-induced inflammation. The multi-functional protein scavenger receptor CD36 has also been shown to participate in inflammation. However, the molecular mechanisms underlying the interactions between CD36 and GLA or LA in LPS-induced inflammation remain unclear. We used small interfering RNA and adenoviral systems to manipulate CD36 expression in primary goat mammary gland epithelial cells (pGMECs), and the results showed that nuclear factor kappa B (NF-κB) levels were significantly decreased by CD36 receptor signaling following treatment with GLA but not LA. GLA inhibited NF-κB activation in LPS-induced pGMECs. However, silencing CD36 or deleting its fatty acid-binding domain blocked the anti-inflammatory effects of GLA, resulting in an increase in NF-κB activation and disrupting its localization during LPS-induced inflammation. The activity of the cytokines IL-1β, IL-6, and TNF-α, which act downstream of NF-κB, was also modulated when CD34 expression was manipulated by the addition of GLA in LPS-induced pGMECs. Our data suggest that GLA, but not LA, may interact with the CD36 fatty acid-binding domain to regulate the activation and localization of NF-κB in LPS-induced pGMECs.
Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Duoyao
D
Cao
Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China. luojun@nwsuaf.edu.cn.
Jun
J
Luo
Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
WenJuan
W
Zang
Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Dekun
D
Chen
Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Huifen
H
Xu
Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Huaiping
H
Shi
Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, Shaanxi, China.
Xiaoqi
X
Jing
D000818:Animals; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006041:Goats; D007249:Inflammation / Q000209:etiology* / Q000473:pathology; D008070:Lipopolysaccharides; D008321:Mammary Glands, Animal / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D017962:alpha-Linolenic Acid / Q000494:pharmacology; D017965:gamma-Linolenic Acid / Q000494:pharmacology*
D018955:CD36 Antigens; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D017962:alpha-Linolenic Acid; D017965:gamma-Linolenic Acid
CD36; gamma-linolenic acid; inflammation; primary goat mammary gland epithelial cells