MicroRNA-mediated calcineurin signaling activation induces CCL2, CCL3, CCL5, IL8, and chemotactic activities in 4,4′-methylene diphenyl diisocyanate exposed macrophages

Lin, Chen-Chung; Law, Brandon F.; Hettick, Justin M.

doi:10.1080/00498254.2021.2005851

Cited by 8 publications

(5 citation statements)

References 87 publications

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“…Our review of other studies found that the regulation of miR‐370 on EMT‐TFs has not been reported yet. MicroRNA‐381 was reported to influence IL‐8 expression, indicating that miR‐381 might be an upstream factor of IL‐8 22 . Based on the above results, we chose miR‐370‐3p as the candidate gene for further study (Figure S2, S5).…”

Section: Resultsmentioning

confidence: 99%

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Hsa‐microRNA‐370‐3p targeting Snail and Twist1 suppresses IL‐8/STAT3‐driven hepatocellular carcinoma metastasis

Peng

Chen

et al. 2022

Cancer Science

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The pro‐inflammatory factor interleukin‐8 (IL‐8) is related to poor prognosis in hepatocellular carcinoma (HCC) patients. Interleukin‐8 enhanced HCC invasion by upregulating Snail and Twist1, whether this modulation relies on microRNAs (miR) is unclear. In this study, hsa‐miR‐370‐3p was screened as candidate miRNA targeting Snail and Twist1, and its expression was downregulated by IL‐8. Luciferase assays and RNA electrophoretic mobility shift assays were used to evaluate the interaction between miR‐370‐3p and targeted mRNAs. Coimmunoprecipitation, luciferase, and ChIP assays were undertaken to investigate the mechanisms underlying IL‐8‐mediated modification of miR‐370‐3p. Gain‐ and loss‐of‐function studies, Transwell assays, and a xenograft nude mouse model were used to investigate pro‐ and antitumor activities. Interleukin‐8 and miR‐370‐3p levels were analyzed for clinical relevance in HCC patients. Our results showed that HCC patients with high levels of IL‐8 experienced more metastasis and shorter survival. Interleukin‐8 induced epithelial–mesenchymal transition and promoted liver cancer cell migration, invasion, and metastasis both in vitro and in vivo. MicroRNA‐370‐3p interacted with its cognate mRNA within the 3′‐UTR regions of Twist1 and Snail mRNA directly and specifically and attenuated IL‐8 protumoral effects on liver cancer cells. Interleukin‐8 negatively modulated miR‐370‐3p through signal transducer and activator of transcription 3 (STAT3) activation by recruiting histone deacetylase 1 (HDAC1) to miR‐370‐3p promoter. The STAT3 and HDAC antagonists inhibited liver cancer cell migration and invasion. Patients with high miR‐370‐3p and low IL‐8 levels had longer overall survival. In conclusion, our study elucidated a novel axis IL‐8/STAT3/miR‐370‐3p/Twist1 and Snail relying on HDAC1 recruitment, which showed both diagnostic and therapeutic potentials of miR‐370‐3p in HCC metastasis.

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Section: Resultsmentioning

confidence: 99%

“…MicroRNA-381 was reported to influence IL-8 expression, indicating that miR-381 might be an upstream factor of IL-8. 22 Based on the above results, we chose miR-370-3p as the candidate gene for further study (Figure S2, S5).…”

Section: Identification Of Emt-tfs Targeting Mirnamentioning

confidence: 99%

Hsa‐microRNA‐370‐3p targeting Snail and Twist1 suppresses IL‐8/STAT3‐driven hepatocellular carcinoma metastasis

Peng

Chen

et al. 2022

Cancer Science

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“…FK506 aka tacrolimus, a calcineurin inhibitor, has recently been shown to attenuate human myeloid responses to MDI in vitro. 90 FKBP5 is known to directly interact with IFI44 (also increased in MDI exposed/sensitized mice) to modify innate immune responses via IRF7 and IRF3. b) ZBTB16 is consistently down regulated in numerous ovalbumin and TH2 cytokine (IL-13, IL4)-driven mouse asthma models, but is increased in MDI-sensitized mice following exposure.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Gene expression in the present MDI asthma pathology model showed substantial overlap with that documented in prior studies with the prototypic HMW ovalbumin allergen; however, several differences were particularly notable. MDI-induced increases in the FK506 binding protein-5 (FKBP5) gene transcript. FK506 aka tacrolimus, a calcineurin inhibitor, has recently been shown to attenuate human myeloid responses to MDI in vitro . FKBP5 is known to directly interact with IFI44 (also increased in MDI exposed/sensitized mice) to modify innate immune responses via IRF7 and IRF3. ZBTB16 is consistently down regulated in numerous ovalbumin and TH2 cytokine (IL-13, IL4)-driven mouse asthma models, but is increased in MDI-sensitized mice following exposure .…”

Section: Discussionmentioning

confidence: 99%

“…MDI-induced increases in the FK506 binding protein-5 (FKBP5) gene transcript. FK506 aka tacrolimus, a calcineurin inhibitor, has recently been shown to attenuate human myeloid responses to MDI in vitro . FKBP5 is known to directly interact with IFI44 (also increased in MDI exposed/sensitized mice) to modify innate immune responses via IRF7 and IRF3.…”

Section: Discussionmentioning

confidence: 99%

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Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA-1 in Pathologic Responses to Diisocyanate

Wisnewski,

Liu

2024

Chem. Res. Toxicol.

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Mechanisms underlying methylene diphenyl diisocyanate (MDI) and other low molecular weight chemical-induced asthma are unclear and appear distinct from those of high molecular weight (HMW) allergen-induced asthma. We sought to elucidate molecular pathways that differentiate asthma-like pathogenic vs nonpathogenic responses to respiratory tract MDI exposure in a murine model. Lung gene expression differences in MDI exposed immune-sensitized and nonsensitized mice vs unexposed controls were measured by microarrays, and associated molecular pathways were identified through bioinformatic analyses and further compared with published studies of a prototypic HMW asthmagen (ovalbumin). Respiratory tract MDI exposure significantly altered lung gene expression in both nonsensitized and immune-sensitized mice, vs controls. Fifty-three gene transcripts were altered in all MDI exposed lung tissue vs controls, with levels up to 10-fold higher in immunesensitized vs nonsensitized mice. Gene transcripts selectively increased in MDI exposed immune-sensitized animals were dominated by chitinases and chemokines and showed substantial overlap with those increased in ovalbumin-induced asthma. In contrast, MDI exposure of nonsensitized mice increased type I interferon stimulated genes (ISGs) in a pattern reflecting deficiency in adenosine deaminase acting against RNA (ADAR-1), an important regulator of innate, as well as "sterile" or autoimmunity triggered by tissue damage. Thus, MDI-induced changes in lung gene expression were identified that differentiate nonpathogenic innate responses in nonsensitized hosts from pathologic adaptive responses in immunesensitized hosts. The data suggest that MDI alters unique biological pathways involving ISGs and ADAR-1, potentially explaining its unique immunogenicity/allergenicity.

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Non-coding RNA regulation of macrophage function in asthma

Tian,

Gao,

Yang

et al. 2023

Cellular Signalling

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MicroRNA-mediated calcineurin signaling activation induces CCL2, CCL3, CCL5, IL8, and chemotactic activities in 4,4′-methylene diphenyl diisocyanate exposed macrophages

Cited by 8 publications

References 87 publications

Hsa‐microRNA‐370‐3p targeting Snail and Twist1 suppresses IL‐8/STAT3‐driven hepatocellular carcinoma metastasis

Hsa‐microRNA‐370‐3p targeting Snail and Twist1 suppresses IL‐8/STAT3‐driven hepatocellular carcinoma metastasis

Lung Gene Expression Suggests Roles for Interferon-Stimulated Genes and Adenosine Deaminase Acting against RNA-1 in Pathologic Responses to Diisocyanate

Non-coding RNA regulation of macrophage function in asthma

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