title: Lectin-like ox-LDL receptor-1 (LOX-1)-Toll-like receptor 4 (TLR4) interaction and autophagy in CATH.a differentiated cells exposed to angiotensin II.
abstract: Toll-like receptors (TLRs) play an essential role in innate immune response. Expression of TLRs has also been linked to autophagy. As the main receptor for oxidized low-density lipoprotein (ox-LDL) on the cell surface, lectin-like ox-LDL receptor-1 (LOX-1) is upregulated by proinflammatory cytokines and has been linked to the development of autophagy. However, the relationship between LOX-1, autophagy, and TLR4 in neurons has not been defined. Here, we show that Angiotensin II (Ang II) treatment of CATH.a differentiated neuronal cells resulted in the expression of TLR4 (and associated signals MyD88 and Toll/interleukin-1 receptor domain-containing adapter-inducing interferon (TRIF)), LOX-1 autophagy. LOX-1 knockdown (transfection with specific small interfering RNA (siRNA)) resulted in reduced expression of TLR4 (and associated signals MyD88 and TRIF) and P-P38 mitogen-activated protein kinase (MAPK) and autophagy. TLR4 knockdown with siRNA resulted in reduced LOX-1 expression and autophagy, indicating a positive feedback between LOX-1 and TLR4. Knockdown of TRIF as well as MyD88 or inhibition of P38 MAPK also inhibited the expression of LOX-1 and TLR4 and autophagy. Importantly, pretreatment with 3-methyladenine (autophagy inhibitor) enhanced while rapamycin (autophagy inducer) decreased the expression of LOX-1, TLR4, and P-P38 MAPK. These studies suggest the presence of a bidirectional link between LOX-1and TLR4 in cultured CATH.a differentiated cells exposed to Ang II with an important role for autophagy in this link.
authors.affiliation: Central Arkansas Veterans Healthcare System and the University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Zufeng
authors.initials: Z
authors.lastname: Ding
authors.forename: Shijie
authors.initials: S
authors.lastname: Liu
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Magomed
authors.initials: M
authors.lastname: Khaidakov
authors.forename: Yao
authors.initials: Y
authors.lastname: Dai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Deng
authors.forename: Yubo
authors.initials: Y
authors.lastname: Fan
authors.forename: David
authors.initials: D
authors.lastname: Xiang
authors.forename: Jawahar L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D002395:Catecholamines; C495138:Olr1 protein, mouse; D051127:Scavenger Receptors, Class E; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000804:Angiotensin II