Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes

Song, Chongmin; Hsu, Kang; Yamen, Eric; Yan, Wei; Fock, Jianyi; Witting, Paul K.; Geczy, Carolyn L.; Freedman, Stephen B.

doi:10.1016/j.hlc.2009.05.613

Cited by 32 publications

(50 citation statements)

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“…These findings suggest the close interrelationship between hs-CRP and WBC counts in our subjects and could support the notion that WBCs release MCP-1 into the circulation. 36 In the present study, male sex and age were independently associated with circulating MCP-1 levels. The results were consistent with the previous observations of Inadera et al, 37 who showed that circulating MCP-1 levels were positively associated with age and tended to be higher in males than females in healthy Japanese subjects.…”

Section: Discussionsupporting

confidence: 49%

High White Blood Cell Count and Low Estimated Glomerular Filtration Rate Are Independently Associated With Serum Level of Monocyte Chemoattractant Protein‐1 in a General Population

Fukami

Yamagishi

Adachi

et al. 2011

Clinical Cardiology

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Background: Monocyte chemoattractant protein-1 (MCP-1) plays a role in cardiovascular disease (CVD) and renal injury. Recent clinical studies have suggested that circulating levels of MCP-1 could be a biomarker of atherosclerosis and future cardiovascular events in humans. Because chronic kidney disease (CKD) is one of the risk factors of CVD, it is conceivable that elevated MCP-1 levels may link the increased risk of CVD in CKD patients. However, as far as we know, in addition to well-known traditional risk factors for atherosclerosis, whether renal dysfunction could be independently associated with the elevation of MCP-1 levels in a general population remains unknown. Therefore, we examined here which anthropometric and metabolic variables, including renal function, could be independent correlates of circulating levels of MCP-1 in a general population. Hypothesis:We hypothesized that renal function was one of the independent correlates of serum MCP-1 levels.Methods: A total of 860 Japanese residents (318 males and 542 females, mean age 65.4 ± 9.8 years) in a small fishing community underwent a complete history and physical examination with determination of blood chemistries, including serum levels of MCP-1.Results: Mean MCP-1 levels were 281.4 pg/mL. Multiple stepwise regression analyses revealed that male sex (P < 0.0001), age (P = 0.03), estimated glomerular filtration rate (eGFR) (P < 0.0001, inversely), and white blood cell count (P = 0.037) were independently associated with MCP-1 levels.Conclusions: The present study demonstrated for the first time that other than white blood cell count, eGFR was an independent correlate of serum levels of MCP-1 in a Japanese general population. Elevated MCP-1 levels may partly explain the increased risk of CVD in CKD patients.

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Section: Discussionsupporting

confidence: 49%

High White Blood Cell Count and Low Estimated Glomerular Filtration Rate Are Independently Associated With Serum Level of Monocyte Chemoattractant Protein‐1 in a General Population

Fukami

Yamagishi

Adachi

et al. 2011

Clinical Cardiology

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“…We also found that ANRIL levels in PBMCs did not have significant correlations with serum IL6/IL8 levels although such a correlation is indeed observed within the PBMC cells. Since PBMCs might not be the only source of the serum IL6/IL8, [51][52][53] thus it is reasonable that serum levels of these 2 cytokines may not well reflect changes of ANRIL in PBMCs. The ANRIL modulated fluctuation of IL6/IL8 might actually become functionally relevant either within these cells, or when the PMBCs are present in certain more enclosed spaces where PMBCs become the major source of IL6/IL8.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

et al. 2015

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Antisense Noncoding RNA in the INK4 Locus (ANRIL) is the prime candidate gene at Chr9p21, the welldefined genetic risk locus associated with multiple human diseases including coronary artery disease (CAD), while little is known regarding its role in the pathological processes. Endothelial dysfunction triggers atherosclerotic processes that are causatively linked to CAD. To evaluate the function of ANRIL in human endothelial cells (ECs), we examined ANRIL expression under pathological stimuli and found ANRIL was markedly induced by pro-inflammatory factors. Loss-of-function and chromatin immunoprecipitation approaches revealed that NF-kB mediates TNF-a induced ANRIL expression. RNA sequencing revealed that ANRIL silencing dysregulated expression of inflammatory genes including IL6 and IL8 under TNF-a treatment. We explored the regulatory mechanism of ANRIL on IL6/8 and found that Yin Yang 1 (YY1), an ANRIL binding transcriptional factor revealed by RNA immunoprecipitation, was required for IL6/8 expression under TNF-a treatment. YY1 was enriched at promoter loci of IL6/8 and ANRIL silencing impaired the enrichment, indicating a cooperation between ANRIL and YY1 in the regulation of inflammatory genes. For the first time, we establish the connection between ANRIL and NF-kB pathway and show that ANRIL regulates inflammatory responses through binding with YY1. The newly identified TNF-a-NF-kB-ANRIL/YY1-IL6/8 pathway enhances understanding of the etiology of CAD and provides potential therapeutic target for treatment of CAD.

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“…5D). Because PI3K and p38MAPK are known to play a role in IL-1b production (36)(37)(38)(39)(40) and IRAK can also activate p38MAPK (9), we evaluated PMA-induced IL-1b production in the presence of SB 202190 (p38MAPK INH) and LY294002 (PI3K INH) (Fig. 5D).…”

Section: Pma Induces Il-1b Production In a Jnk-dependent But Nf-kb-inmentioning

confidence: 99%

IL-1R–Associated Kinase-1 Mediates Protein Kinase Cδ-Induced IL-1β Production in Monocytes

Tiwari

Singh

et al. 2011

The Journal of Immunology

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The role of IL-1R–associated kinase (IRAK)1 and its interaction with protein kinase C (PKC)δ in monocytes to regulate IL-1β production has not been reported so far. The present study thus investigates such mechanisms in the THP1 cell line and human monocytes. PMA treatment to THP1 cells induced CD11b, TLR2, TLR4, CD36, IRAK1, IRAK3, and IRAK4 expression, IRAK1 kinase activity, PKCδ and JNK phosphorylation, AP-1 and NF-κB activation, and secretory IL-1β production. Moreover, PMA-induced IL-1β production was significantly reduced in the presence of TLR2, TLR4, and CD11b Abs. Rottlerin, a PKCδ-specific inhibitor, significantly reduced PMA-induced IL-1β production as well as CD11b, TLR2 expression, and IRAK1–JNK activation. In PKCδ wild-type overexpressing THP1 cells, IRAK1 kinase activity and IL-1β production were significantly augmented, whereas recombinant inactive PKCδ and PKCδ small interfering RNA significantly inhibited basal and PMA-induced IRAK1 activation and IL-1β production. Endogenous PKCδ–IRAK1 interaction was observed in quiescent cells, and this interaction was regulated by PMA. IRAK1/4 inhibitors, their small interfering RNAs, and JNK inhibitor also attenuated PMA-induced IL-1β production. NF-κB activation inhibitor and SN50 peptide inhibitor, however, failed to affect PMA-induced IL-1β production. A similar role of IRAK1 in IL-1β production and its regulation by PKCδ was evident in the primary human monocytes, thus signifying the importance of our finding. To our knowledge, the results obtained demonstrate for the first time that IRAK1 and PKCδ functionally interact to regulate IL-1β production in monocytic cells. A novel mechanism of IL-1β production that involves TLR2, CD11b, and the PKCδ/IRAK1/JNK/AP-1 axis is thus being proposed.

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Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes

Cited by 32 publications

References 0 publications

High White Blood Cell Count and Low Estimated Glomerular Filtration Rate Are Independently Associated With Serum Level of Monocyte Chemoattractant Protein‐1 in a General Population

High White Blood Cell Count and Low Estimated Glomerular Filtration Rate Are Independently Associated With Serum Level of Monocyte Chemoattractant Protein‐1 in a General Population

Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway

IL-1R–Associated Kinase-1 Mediates Protein Kinase Cδ-Induced IL-1β Production in Monocytes

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