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PKCδ-IRAK1 axis regulates oxidized LDL induced IL-1β prod uction in monocytes

หน่วยงาน Central Drug Research Institute (CDRI), India

รายละเอียด

ชื่อเรื่อง : PKCδ-IRAK1 axis regulates oxidized LDL induced IL-1β prod uction in monocytes
นักวิจัย : Tiwari, R L , Singh, Vishal , Singh, Ankita , Rana, Minakshi , Verma, Anupam , Kothari, Nikhil , Kohli, Monica , Bogra, Jaishri , Dikshit, Madhu , Barthwal, M K
คำค้น : Oxidized-Low Density Lipoprotein , Protein Kinase C Delta , Interleukin-1 Receptor Associated Kinase , Inflammation, Monocytes
หน่วยงาน : Central Drug Research Institute (CDRI), India
ผู้ร่วมงาน : -
ปีพิมพ์ : 2557
อ้างอิง : Journal of Lipid Research, 2014, 55(7):1226-1244 , http://hdl.handle.net/123456789/1378
ที่มา : -
ความเชี่ยวชาญ : -
ความสัมพันธ์ : CSIR-CDRI Communication No. 8687
ขอบเขตของเนื้อหา : -
บทคัดย่อ/คำอธิบาย :

Present study examined the role of IL-1R-associated kinase (IRAK) and protein kinase C (PKC) in Oxidized LDL (Ox-LDL) induced monocyte IL-1β production. In THP1 cells Ox-LDL induced time dependent secretory IL-1β, IRAK1 activity, IRAK4, IRAK3, CD36 protein expression, PKCδ-JNK1 phosphorylation and AP1 activation. IRAK1/4 siRNA and inhibitor attenuated Ox-LDL induced secreted IL-1β and pro-IL-1β mRNA, pro and mature IL-1β protein expression respectively. DPI (NADPH oxidase inhibitor) and NAC (Free radical scavenger) attenuated Ox-LDL induced reactive oxygen species (ROS) generation, caspase 1 activity and pro and mature IL-1β expression. Ox-LDL induced secretory IL-1β production was abrogated in presence of JNK Inhibitor II, Tanshinone IIa, Ro-31-8220, Go6976, Rottlerin and PKCδ siRNA. PKCδ siRNA, attenuated Ox-LDL induced increase in IRAK1 kinase activity, JNK1 phosphorylation and AP1 activation. In THP-1 macrophages, CD36, TLR2, 4, 6 and PKCδ SiRNA prevented Ox-LDL induced PKCδ, IRAK1 activation and IL-1β production. Enhanced Ox-LDL and IL-1β in SIRS patient plasma demonstrated positive correlation among each other and with disease severity scores. Ox-LDL containing plasma induced PKCδ, IRAK1 phosphorylation and IL-1β production in CD36, TLR 2,4 and 6 dependent manner in primary human monocytes. Results suggest involvement of CD36, TLR2,4,6 and PKCδ-IRAK1-JNK1-AP-1 axis in Ox-LDL induced IL-1β production.

บรรณานุกรม :
Tiwari, R L , Singh, Vishal , Singh, Ankita , Rana, Minakshi , Verma, Anupam , Kothari, Nikhil , Kohli, Monica , Bogra, Jaishri , Dikshit, Madhu , Barthwal, M K . (2557). PKCδ-IRAK1 axis regulates oxidized LDL induced IL-1β prod uction in monocytes.
    : Central Drug Research Institute (CDRI), India.
Tiwari, R L , Singh, Vishal , Singh, Ankita , Rana, Minakshi , Verma, Anupam , Kothari, Nikhil , Kohli, Monica , Bogra, Jaishri , Dikshit, Madhu , Barthwal, M K . 2557. "PKCδ-IRAK1 axis regulates oxidized LDL induced IL-1β prod uction in monocytes".
    : Central Drug Research Institute (CDRI), India.
Tiwari, R L , Singh, Vishal , Singh, Ankita , Rana, Minakshi , Verma, Anupam , Kothari, Nikhil , Kohli, Monica , Bogra, Jaishri , Dikshit, Madhu , Barthwal, M K . "PKCδ-IRAK1 axis regulates oxidized LDL induced IL-1β prod uction in monocytes."
    : Central Drug Research Institute (CDRI), India, 2557. Print.
Tiwari, R L , Singh, Vishal , Singh, Ankita , Rana, Minakshi , Verma, Anupam , Kothari, Nikhil , Kohli, Monica , Bogra, Jaishri , Dikshit, Madhu , Barthwal, M K . PKCδ-IRAK1 axis regulates oxidized LDL induced IL-1β prod uction in monocytes. : Central Drug Research Institute (CDRI), India; 2557.