cAMP induces CD14 expression in murine macrophages via increased transcription

Liu, Shubing; Morris, Sidney M.; Nie, Suhua; Shapiro, Richard A.; Billiar, Timothy R.

doi:10.1002/jlb.67.6.894

Cited by 12 publications

(9 citation statements)

References 70 publications

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“…While EP2 and EP4 activation by PGE 2 promotes suppressive effects via cAMP/PKA/CREB pathway ( 47 ), TsV induces a different molecular signaling pathway that culminates with pro-inflammatory cytokine production via cAMP/PKA/NF-κB ( 3 , 11 ). Interestingly, PGE 2 induces CD14 expression in macrophages via cAMP/PKA ( 48 ), suggesting a regulatory loop between cAMP and CD14, and control over IL-1β-mediated inflammation. Cd14 −/− derived peritoneal macrophages produce more LTB 4 than wild-type cells when stimulated with TsV ( 11 ), while the effects of U75302, a BLT1 antagonist, or forskolin (a PKA activator), were only observed using higher concentrations of these compounds.…”

Section: Discussionmentioning

confidence: 99%

CD36 Shunts Eicosanoid Metabolism to Repress CD14 Licensed Interleukin-1β Release and Inflammation

et al. 2018

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Interleukin (IL)-1β is a potential target for treatment of several inflammatory diseases, including envenomation by the scorpion Tityus serrulatus. In this context, bioactive lipids such as prostaglandin (PG)E2 and leukotriene (LT)B4 modulate the production of IL-1β by innate immune cells. Pattern recognition receptors (PRRs) that perceive T. serrulatus venom (TsV), and orchestrate LTB4, PGE2, and cyclic adenosine monophosphate (cAMP) production to regulate IL-1β release are unknown. Furthermore, molecular mechanisms driving human cell responses to TsV remain uncharacterized. Here, we identified that both CD14 and CD36 control the synthesis of bioactive lipids, inflammatory cytokines, and mortality mediated by TsV. CD14 induces PGE2/cAMP/IL-1β release and inflammation. By contrast, CD36 shunts eicosanoid metabolism toward production of LTB4, which represses the PGE2/cAMP/IL-1β axis and mortality. Of importance, the molecular mechanisms observed in mice strongly correlate with those of human cell responses to TsV. Overall, this study provides major insights into molecular mechanisms connecting CD14 and CD36 with differential eicosanoid metabolism and inflammation mediated by IL-1β.

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Section: Discussionmentioning

confidence: 99%

CD36 Shunts Eicosanoid Metabolism to Repress CD14 Licensed Interleukin-1β Release and Inflammation

et al. 2018

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“…For example, up-regulation of CD14 has been reported in response to IL-1β [127], TNF-α [128], cAMP, and protein kinase A [129], while IL-4 [130,131], GM-CSF [132], TGF-β1 [133] and glucocorticoids [134] have been shown to down-regulate CD14 expression. Recently, Wheeler and Thurman demonstrated that up-regulation of CD14 expression in murine hepatocytes and Kupffer cells was oxidant-dependent, requiring activation of the redox-sensitive transcription factor AP-1, and was blunted by over-expression of Cu/Zn superoxide dismutase (Cu/Zn SOD) [135].…”

Section: Regulation Of Cd14 Expressionmentioning

confidence: 99%

Endotoxin, TLR4 Signaling and Vascular Inflammation: Potential Therapeutic Targets in Cardiovascular Disease

Stoll

Denning

Weintraub

2006

CPD

101

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Cardiovascular disease ranks among the leading causes of morbidity and mortality in adult populations in the Western world. Significant progress in understanding the etiology of cardiovascular disease has come from recent recognition that chronic inflammation plays a key role in its development. The principal mediators of this inflammatory response, and the mechanisms by which they work, however, are incompletely understood. Moreover, the complex nature of the inflammatory response poses significant challenges to the development of effective and targeted treatments. Potentially promising targets to reduce inflammation in atherosclerosis include Toll-like receptor (TLR) pathways and anti-inflammatory factors that modulate TLR signaling. In this review, we outline studies that provide insight into the links between cardiovascular disease and inflammation, focusing on innate immunity and endotoxin/TLR4 signaling. We also discuss the contribution of specific host immune/inflammatory responses to atherogenesis, and describe cellular signaling pathways (lipopolysaccharide-binding protein [LBP], CD14, MD-2, TLR4, MyD88, and NF-kappaB, among others) that play key roles in innate immune signaling. Finally, we discuss the therapeutic potential of modulating these cellular signaling pathways as future strategies for the prevention and treatment of cardiovascular disease, including such approaches as specific targeting of the TLR4 signaling pathway, antibiotic therapy, drug classes with broad anti-inflammatory activity (statins, thiazolidinediones), and the potential of vaccine development. Because of the complexity of the links between low-level chronic infections, inflammation, and atherosclerosis, treatment and prevention of cardiovascular disease will likely require an integrated approach that utilizes a combination of these strategies to target the underlying inflammatory processes.

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“…We found that Lrch4 regulates the raft molecules GM1 and CD14, the latter at the level of transcript abundance. Intracellular mediators of CD14 transcription have been defined, including cAMP (40) and transcription factors, such as AP1, Sp1, C/EBP, and STAT1 (41-43), several of these regulating CD14 in response to extracellular signals. Similarly, although rafts are thought to be assembled through complex protein-lipid interactions that begin in the Golgi (30), raft abundance on the cell surface as assessed by CtB is also sensitive to extracellular signals.…”

Section: Lrch4 Regulates Tlrsmentioning

confidence: 99%

Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response

Aloor

Azzam

Guardiola

et al. 2019

Journal of Biological Chemistry

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cAMP induces CD14 expression in murine macrophages via increased transcription

Cited by 12 publications

References 70 publications

CD36 Shunts Eicosanoid Metabolism to Repress CD14 Licensed Interleukin-1β Release and Inflammation

CD36 Shunts Eicosanoid Metabolism to Repress CD14 Licensed Interleukin-1β Release and Inflammation

Endotoxin, TLR4 Signaling and Vascular Inflammation: Potential Therapeutic Targets in Cardiovascular Disease

Leucine-rich repeats and calponin homology containing 4 (Lrch4) regulates the innate immune response

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