MicroRNA-155 Is Required for <i>Mycobacterium bovis</i> BCG-Mediated Apoptosis of Macrophages

Ghorpade, Devram Sampat; Leyland, Rebecca; Kurowska‐Stolarska, Mariola; Patil, Shripad A.; Balaji, Kithiganahalli Narayanaswamy

doi:10.1128/mcb.06597-11

Cited by 137 publications

(124 citation statements)

References 71 publications

(73 reference statements)

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Upregulation of BCL6 in lesional Mir155 -/-macrophages repressed CCL2 expression, which is known to promote the recruitment of monocytes to atherosclerotic plaques (18). In addition to its immunoregulatory functions, miR-155 can enhance or prevent the apoptosis of infected macrophages (52,53). However, we did not observe any effect of miR-155 on the apoptosis of lesional macrophages.…”

Section: Discussioncontrasting

confidence: 50%

MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages

Nazari-Jahantigh¹,

Wei²,

Noels³

et al. 2012

J. Clin. Invest.

463

424

View full text Add to dashboard Cite

Macrophages in atherosclerotic plaques drive inflammatory responses, degrade lipoproteins, and phagocytose dead cells. MicroRNAs (miRs) control the differentiation and activity of macrophages by regulating the signaling of key transcription factors. However, the functional role of macrophage-related miRs in the immune response during atherogenesis is unknown. Here, we report that miR-155 is specifically expressed in atherosclerotic plaques and proinflammatory macrophages, where it was induced by treatment with mildly oxidized LDL (moxLDL) and IFN-γ. Leukocyte-specific Mir155 deficiency reduced plaque size and number of lesional macrophages after partial carotid ligation in atherosclerotic (Apoe -/-) mice. In macrophages stimulated with moxLDL/IFN-γ in vitro, and in lesional macrophages, loss of Mir155 reduced the expression of the chemokine CCL2, which promotes the recruitment of monocytes to atherosclerotic plaques. Additionally, we found that miR-155 directly repressed expression of BCL6, a transcription factor that attenuates proinflammatory NF-κB signaling. Silencing of Bcl6 in mice harboring Mir155 -/-macrophages enhanced plaque formation and CCL2 expression. Taken together, these data demonstrated that miR-155 plays a key role in atherogenic programming of macrophages to sustain and enhance vascular inflammation.

show abstract

Section: Discussioncontrasting

confidence: 50%

MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages

Nazari-Jahantigh¹,

Wei²,

Noels³

et al. 2012

J. Clin. Invest.

463

424

View full text Add to dashboard Cite

show abstract

“…As described earlier in several published reports, targeting the adaptor molecules of the TLR signaling pathway is one of the mechanisms involved in regulating TLR-mediated inflammatory gene expression (50). It has been shown that MyD88, one of the adaptor molecules associated with TLR signaling pathways, is targeted to proteosomal degradation by E3 ligases like Smurf (24).…”

Section: Discussionmentioning

confidence: 99%

The WNT Signaling Pathway Contributes to Dectin-1-Dependent Inhibition of Toll-Like Receptor-Induced Inflammatory Signature

Trinath

Holla

Mahadik

et al. 2014

Molecular and Cellular Biology

Self Cite

View full text Add to dashboard Cite

Macrophages regulate cell fate decisions during microbial challenges by carefully titrating signaling events activated by innate receptors such as dectin-1 or Toll-like receptors (TLRs). Here, we demonstrate that dectin-1 activation robustly dampens TLRinduced proinflammatory signature in macrophages. Dectin-1 induced the stabilization of ␤-catenin via spleen tyrosine kinase (Syk)-reactive oxygen species (ROS) signals, contributing to the expression of WNT5A. Subsequently, WNT5A-responsive protein inhibitors of activated STAT (PIAS-1) and suppressor of cytokine signaling 1 (SOCS-1) mediate the downregulation of IRAK-1, IRAK-4, and MyD88, resulting in decreased expression of interleukin 12 (IL-12), IL-1␤, and tumor necrosis factor alpha (TNF-␣). In vivo activation of dectin-1 with pathogenic fungi or ligand resulted in an increased bacterial burden of Mycobacteria, Klebsiella, Staphylococcus, or Escherichia, with a concomitant decrease in TLR-triggered proinflammatory cytokines. All together, our study establishes a new role for dectin-1-responsive inhibitory mechanisms employed by virulent fungi to limit the proinflammatory environment of the host.

show abstract

“…MTOR promotes etoposideinduced DNA damage response through activation of CREB1 cAMP, which can trigger the activation of CREB1, has been reported to sensitize cells to proapoptotic agents. 29 Moreover, CREB1 has been implicated in the enhanced expression of CCND1 (cyclin D1), 45 BID, 46 TP53, and CDKN1A/p21. 30,47 Since cAMP, CCND1, BID, TP53, and CDKN1A are involved in the DNA damage response, 46,[48][49][50][51] we proposed that the enhanced phosphorylation and accumulation of CREB1 might be necessary to mediate the effect of constitutive MTOR activation on DNA damage and subsequent apoptosis in response to etoposide.…”

Section: Mtor Enhances Etoposide-induced Creb1 Activationmentioning

confidence: 99%

“…29 Moreover, CREB1 has been implicated in the enhanced expression of CCND1 (cyclin D1), 45 BID, 46 TP53, and CDKN1A/p21. 30,47 Since cAMP, CCND1, BID, TP53, and CDKN1A are involved in the DNA damage response, 46,[48][49][50][51] we proposed that the enhanced phosphorylation and accumulation of CREB1 might be necessary to mediate the effect of constitutive MTOR activation on DNA damage and subsequent apoptosis in response to etoposide. By silencing Creb1 gene expression with RNA interference in MTOR-hyperactivated MEFs, we found that suppression of CREB1 inhibited hyperactive MTOR-enhanced DNA damage as evidenced by decreased γ-H2A.X expression ( Fig.…”

Section: Mtor Enhances Etoposide-induced Creb1 Activationmentioning

confidence: 99%