The Peritoneal Macrophages in Inflammatory Diseases and Abdominal Cancers

Liu, Ting; Liu, Fang; Peng, Leiwen; Chang, Li; Jiang, Yongmei

doi:10.3727/096504017x15130753659625

Cited by 30 publications

(19 citation statements)

References 26 publications

(41 reference statements)

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“…On the flip side, PD-1 signaling inhibited BHLHE40 expression in TIL [138]. Peritoneal macrophages are known to play immunological functions in abdominal cancers [139]. BHLHE40 is highly expressed in large peritoneal macrophages (LPM) [140].…”

Section: Immunomodulatory Effects Of Bhlhe40 In Cancermentioning

confidence: 99%

Non-circadian aspects of BHLHE40 cellular function in cancer

2020

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While many genes specifically act as oncogenes or tumor suppressors, others are tumor promoters or suppressors in a context-dependent manner. Here we will review the basic-helix-loop-helix (BHLH) protein BHLHE40, (also known as BHLHB2, STRA13, DEC1, or SHARP2) which is overexpressed in gastric, breast, and brain tumors; and downregulated in colorectal, esophageal, pancreatic and lung cancer. As a transcription factor, BHLHE40 is expressed in the nucleus, where it binds to target gene promoters containing the E-box hexanucleotide sequence, but can also be expressed in the cytoplasm, where it stabilizes cyclin E, preventing cyclin E-mediated DNA replication and cell cycle progression. In different organs BHLHE40 regulates different targets; hence may have different impacts on tumorigenesis. BHLHE40 promotes PI3K/Akt/ mTOR activation in breast cancer, activating tumor progression, but suppresses STAT1 expression in clear cell carcinoma, triggering tumor suppression. Target specificity likely depends on cooperation with other transcription factors. BHLHE40 is activated in lung and esophageal carcinoma by the tumor suppressor p53 inducing senescence and suppressing tumor growth, but is also activated under hypoxic conditions by HIF-1α in gastric cancer and hepatocellular carcinomas, stimulating tumor progression. Thus, BHLHE40 is a multi-functional protein that mediates the promotion or suppression of cancer in a context dependent manner.

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Section: Immunomodulatory Effects Of Bhlhe40 In Cancermentioning

confidence: 99%

Non-circadian aspects of BHLHE40 cellular function in cancer

2020

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“…Regulatory ncRNAs such as miRNAs and lncRNAs have been shown to regulate the expression, stability, and subcellular location of PCGs in a various number of biological processes [ 81 , 82 ]. Nowadays, several studies about the association between miRNAs and KLF5 have been published [ 83 – 85 ]. For example, miR-5195-3p inhibits the proliferation and invasion of human bladder cancer cells by directly targeting KLF5 [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, several studies about the association between miRNAs and KLF5 have been published [ 83 – 85 ]. For example, miR-5195-3p inhibits the proliferation and invasion of human bladder cancer cells by directly targeting KLF5 [ 83 ]. Interestingly, KLF5 acts as a transcription factor, which can regulate the expression of miRNA such as miR-200, to maintain epithelial characteristics and preventing epithelial-mesenchymal transition in epithelial cells [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer

Liao¹,

Chen²,

Zhang³

et al. 2020

Cancer Cell Int

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Background KLF5 is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. KLF5 functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated by KLF5 in CRC are currently unknown. Methods In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of KLF5 in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of KLF5 were then searched for through bioinformatics analysis. We also constructed a regulatory network for KLF5 and annotated its functions. Finally, one of the KLF5 lncRNA targets, SNHG12, was selected to further explore its expression pattern and functions in CRC. Results We were able to identify 19 lncRNA targets of KLF5 and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors AR and HSF1 as the regulatory co-factors of KLF5 through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that KLF5 may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the SNHG12 up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that SNHG12 may play a critical part in CRC tumorigenesis and progression. Additionally, expression of SNHG12 was found to be down-regulated in CRC cell lines when KLF5 expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of SNHG12 and KLF5, further alluding to their regulatory relationship. Conclusions In conclusion, the network analysis of KLF5 targets indicates that SNHG12 may be a significant lncRNA in CRC.

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“…In terms of function, peritoneal macrophages have been attributed with a broad repertoire of functions, with both subsets working in concert to fulfil homeostatic functions such as immunosurveillance of the peritoneal cavity, resolution of inflammation, and clearance of apoptotic debris (Figure 1). 5,14,21,22,24,27,28 Interestingly, in C57BL/6 mice injected intraperitoneally with immune stimulators such as zymosan particles, Trypanosoma cruzi trypomastigotes 15 or LPS from Escherichia coli , 29 LPMs undergo the macrophage disappearance reaction (MDR) (Figure 1), during which they are thought to transiently cluster on the peritoneal mesothelium, 4,15,29–31 thus becoming temporarily near‐undetectable in the peritoneal fluid. The MDR is demonstrated by a clear decrease in the numbers of LPMs present in peritoneal cell suspensions harvested as soon as 24 h, 29 48 h, 32 and up to 4 days 29 after immune stimulation.…”

Section: Peritoneal Immune Cellsmentioning

confidence: 99%

Immunoregulation by type I interferons in the peritoneal cavity

Chuah

Hertzog

Campbell

2021

Journal of Leukocyte Biology

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The peritoneal cavity, a fluid‐containing potential space surrounding the abdominal and pelvic organs, is home to a rich network of immune cells that maintain tissue homeostasis and provide protection against infection. However, under pathological conditions such as peritonitis, endometriosis, and peritoneal carcinomatosis, the peritoneal immune system can become dysregulated, resulting in nonresolving inflammation and disease progression. An enhanced understanding of the factors that regulate peritoneal immune cells under both homeostatic conditions and in disease contexts is therefore required to identify new treatment strategies for these often life‐limiting peritoneal pathologies. Type I interferons (T1IFNs) are a family of cytokines with broad immunoregulatory functions, which provide defense against viruses, bacteria, and cancer. There have been numerous reports of immunoregulation by T1IFNs within the peritoneal cavity, which can contribute to both the resolution or propagation of peritoneal disease states, depending on the specifics of the disease setting and local environment. In this review, we provide an overview of the major immune cell populations that reside in the peritoneal cavity (or infiltrate it under inflammatory conditions) and highlight their contribution to the initiation, progression, or resolution of peritoneal diseases. Additionally, we will discuss the role of T1IFNs in the regulation of peritoneal immune cells, and summarize the results of laboratory studies and clinical trials which have investigated T1IFNs in peritonitis/sepsis, endometriosis, and peritoneal carcinomatosis.

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The Peritoneal Macrophages in Inflammatory Diseases and Abdominal Cancers

Cited by 30 publications

References 26 publications

Non-circadian aspects of BHLHE40 cellular function in cancer

Non-circadian aspects of BHLHE40 cellular function in cancer

Network analysis of KLF5 targets showing the potential oncogenic role of SNHG12 in colorectal cancer

Immunoregulation by type I interferons in the peritoneal cavity

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