ABCA1 Protein Enhances Toll-like Receptor 4 (TLR4)-stimulated Interleukin-10 (IL-10) Secretion through Protein Kinase A (PKA) Activation

Ma, Loretta; Fang, Dong; Zaid, Maryam; Kumar, Ashok; Zha, Xiaohui

doi:10.1074/jbc.m112.413245

Cited by 61 publications

(67 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to the control of intracellular cholesterol levels, LXRs are involved in induction of IL-10 production through protein kinase Adependent pathway [111]. LXRs could also regulate inflammatory response by activating expression of the interferon regulatory factor 8 (IRF8) that in turn cooperate with the transcription factor PU.1 to induce expression of Arg-1 [112].…”

Section: Effects Of Transcription Factors On Macrophage Phenotypementioning

confidence: 99%

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

Chistiakov

Bobryshev

Nikiforov

et al. 2015

International Journal of Cardiology

163

138

View full text Add to dashboard Cite

Section: Effects Of Transcription Factors On Macrophage Phenotypementioning

confidence: 99%

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

Chistiakov

Bobryshev

Nikiforov

et al. 2015

International Journal of Cardiology

163

138

View full text Add to dashboard Cite

“…We propose that, unlike previously described miRNA regulators of TLR cascades, this occurs through an indirect mechanism, namely augmentation of cholesterol-enriched lipid raft membrane microdomains via dual suppression of ABCA1 and ABCG1. ABCA1-dependent lipid raft reduction has previously been reported to decrease proinflammatory cytokines in LPSexposed macrophages (25,33). The present report is, to our knowledge, the first to directly address the impact of miR-33 on TLR-induced inflammation.…”

Section: Mir-33 Regulates the Innate Immune Responsementioning

confidence: 66%

MicroRNA-33 Regulates the Innate Immune Response via ATP Binding Cassette Transporter-mediated Remodeling of Membrane Microdomains

Lai

Azzam

Lin

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

MicroRNAs (miRNAs) 3 are small (ϳ22-nucleotide) noncoding RNAs that regulate gene expression by binding to partially complementary sites in the 3Ј-untranslated regions (UTRs) of specific mRNAs, thereby promoting degradation and/or repressing translation of target mRNAs. The human genome contains Ͼ2500 unique mature miRNAs (1). Because individual miRNAs typically have multiple targets, it is thought that Ͼ60% of all human genes may be subject to regulation by miRNAs (2). The promiscuity of miRNAs for target RNAs is expected to represent a fundamental mechanism of cross-talk and coordination among signaling networks in development, health, and disease.Among the signaling networks that have been shown in recent years to be regulated by miRNAs are the Toll-like receptors (TLRs) of the innate immune system. Multiple TLRs up-regulate miRNAs, including miR-155, miR-146, miR-21, miR-147, and miR-9, whereas activation of TLR4 by lipopolysaccharide (LPS) down-regulates a distinct set of miRNAs (3, 4). In turn, miRNAs "fine tune" the proinflammatory signaling output of TLR cascades by controlling the expression of TLR pathway members (3, 4). Thus, miR-146 suppresses signaling by multiple TLRs via targeting the common signaling hubs IL-1 receptor-associated kinase 1 and TNF receptor-associated factor 6 (5), whereas miR-155 has complex effects, repressing the TLR adaptor myeloid differentiation primary response 88 (MyD88) (6, 7) and TAK1-binding protein 2 (8), an upstream activator of the mitogen-activated protein kinases, but also promoting cytokine expression through actions on other targets (3). Although virtually all known examples of TLR regulation by miRNAs operate through direct targeting of TLR pathway components, it is expected that miRNAs may also indirectly impact the innate immune response by regulating other networks that cross-talk with TLRs.miR-33a and miR-33b (present in primates but absent in rodents and lower species in which miR-33a is simply referred to as "miR-33") are now known to be master regulators of cho-

show abstract

“…It is also noteworthy that Akt2 ablation, not Akt1, is reported to promote alternative activation (M2) in macrophages [49]. We recently show that ABCA1 could similarly promote M2 polarization, parallel to its function in cholesterol efflux [50]. It is not clear yet whether ABCA1 directly modulates Akt activities, particularly the activities of each isoform.…”

Section: Discussionmentioning

confidence: 97%

Akt Inhibition Promotes ABCA1-Mediated Cholesterol Efflux to ApoA-I through Suppressing mTORC1

et al. 2014

Self Cite

View full text Add to dashboard Cite

ATP-binding cassette transporter A1 (ABCA1) plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I), a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.

show abstract

ABCA1 Protein Enhances Toll-like Receptor 4 (TLR4)-stimulated Interleukin-10 (IL-10) Secretion through Protein Kinase A (PKA) Activation

Cited by 61 publications

References 34 publications

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

MicroRNA-33 Regulates the Innate Immune Response via ATP Binding Cassette Transporter-mediated Remodeling of Membrane Microdomains

Akt Inhibition Promotes ABCA1-Mediated Cholesterol Efflux to ApoA-I through Suppressing mTORC1

Contact Info

Product

Resources

About