Table 1 The direct link between TLR4 and miR-155 in the context of different disorders or cell lines

Regulatory activity of miR-155 on TLR4 signaling

Human HaCaT keratinocytes

miR-155 mimic transfection

100 ng for 6 h

TLR4 expression was significantly increased by miR-155 overexpression

Western blot

Psoriasis

[90]

Mouse microglia BV2 cells

miR-155 mimic transfection

1 μmol/L for 24 h

Oxygen–glucose deprivation-induced TLR4 upregulation was promoted and inhibited, respectively, by miR-155 overexpression and knockdown

Western blot

Ischemic brain injury

[92]

miR-155 inhibitor transfection

2 μmol/L for 24 h

Human acute mono-cytic leukemia THP-1 cells and THP-1-derived macrophages

miR-155-3p mimic transfection

15 nM for 12 h

TLR4 was downregulated by miR-155-3p in monocytes and macrophages

qPCR

–

[89]

Mouse brain tissues

miR-155−/− mice

Model animal

Marked expression of TLR4 was observed in ischemic cerebral tissue of WT mice at 24 h after middle cerebral artery occlusion, and this expression was obviously reduced in miR-155−/− mice

Western blot /qPCR

Ischemic brain injury

[92]

Injection of pAdmiR-155 into lateral cerebral ventricle of mice

Single stereotactic injection

TLR4 expression was significantly increased in ischemic cerebral tissue of miR-155-overexpressing mice compared with pAd-infected mice

Western blot /qPCR

Mouse prostate tissues

miR-155−/− mice

Model animal

miR-155−/− mice with prostatitis exhibited the suppressed TLR4/NF-κB pathway as compared with the WT mice with prostatitis

Western blot

Experimental autoimmune prostatitis

[91]

Inductive effect of TLR4 activation on miR-155

Mouse RAW264.7 cells

LPS treatment

100 ng/mL for 0–24 h

Among the miRNAs that were induced the most by LPS, miR-155 was on the top of the list

MicroRNA arrays

–

[93, 105, 106, 110, 123, 135, 136]

It was validated that miR-155 and BIC/primiR-155 expression was increased in a time-dependent manner

Northern blot/qPCR

0–1 μg/mL for 24 h

miR-155 and BIC expression was increased in a dose-dependent manner

qPCR

100 ng/mL for 24 h

In cells transfected with pri-155 promoter, pri-155 promoter was drove fivefold by LPS

Luciferase assay

10 ng/mL for 6 h

Among the LPS-induced miRNAs, miR-155 showed the highest fold change (40-fold)

MicroRNA deep-sequencing

Mouse BMDMs

LPS treatment

100 ng/mL for 0–24 h

The time-dependent induction of BIC transcript and miR-155 by LPS was observed in BMDMs from WT mice

Northern blot/qPCR

–

[93, 105, 110, 123, 129, 135, 136]

0–0.1 μg/mL for 8 h

miR-155 expression was increased in a dose-dependent manner

qPCR

100 ng/mL for 8 h

A strong and prolonged increase of miR-155 expression was induced by LPS in BMDMs without a concomitant increase of pri-miR155

Northern blot/Semi-quantitative RT-PCR

TLR4−/− BMDM

Model cell

LPS-induced miR-155 expression was decreased from approximately 40-fold activation in WT-BMDM to less than twofold in TLR4−/− BMDM

qPCR

Human PBMCs

LPS treatment

100 ng/mL for 0–24 h

miR-155 expression was increased eightfold by LPS in PBMC after 24 h stimulation

qPCR

–

[93, 135]

Human monocytes

LPS treatment

100 ng/mL for 6 and 24 h

miR-155 expression was upregulated by LPS at both timepoints

MicroRNAdeep-sequencing/qPCR

–

[109]

Mouse bone marrow-derived DCs

LPS treatment

1 ug/mL for 24 h

In response to stimulation with LPS, miR-155 expression was upregulated in mature DCs as compared with immature DCs

MicroRNA arrays/qPCR

–

[108]

Human monocyte-derived DCs

LPS treatment

1 ug/mL for 24 h

At 24 h after stimulation, miR-155 expression was upregulated by LPS when compared to cells receiving medium alone

qPCR

–

[107]

Human monocyte-derived Macrophage

LPS treatment

100 ng/mL for 24 h

An increase of miR-155-5p levels induced by LPS was found in monocyte- derived macrophage (fold change ~ 60)

qPCR

–

[132]

Mouse primary microglia

LPS treatment

0.1 or 1 μg/mL for 18 h

LPS treatment at the level of 0.1 or 1 μg/mL lead to a 12-fold or 21-fold increase in the expression of miR-155, respectively

qPCR

Ischemic brain injury

[111, 113]

The miR-155 labelling was significantly more intense in the cytoplasm of microglia cells incubated with LPS than in control cells

In situ hybridization

Mouse microglia N9 cells

LPS treatment

0.1, 0.5 and 1 μg/mL for 18 h and 0.1 μg/mL for different time periods (0.5, 1, 2, 4, 18 and 24 h)

miR-155 expression was induced in a dose-dependent manner, which reached a 25-fold increase in miR-155 levels for the highest LPS concentration tested

qPCR

Ischemic brain injury

[111]

miR-155 levels continued to increase, reaching a maximum at 18 h, but showed a tendency to decrease after an incubation period of 24 h

Mouse microglia BV2 cells

LPS treatment

100 ng/mLfor 4 h

miR-155-3p was the most significantly upregulated miRNA (by 29-fold versus control), followed by miR-155-5p (by 9.7-fold)

MicroRNA sequencing

Brain injury

[112, 113]

20 ng/mL for 24 h

miR-155 expression was significantly increased

qPCR

Mouse kupffer cells (KCs)

LPS treatment

100 ng/mL for 6 and 18 h

Alcohol-induced miR-155 expression was further augmented by in vitro LPS challenge in KCs isolated from alcohol-fed mice compared with pair-fed mice

qPCR

Alcoholic steatohepatitis

[100, 133]

Mouse alveolar macrophages (AMs)

LPS treatment

100 ng/mL for indicated time periods (0–6 h)

miR-155 expression level was dramatically increased in response to LPS stimulation in control AMs

qPCR

Acute lung injury

[128]

Human proximal tubule epithelial HK-2 cells

LPS treatment

5 μg/mL for 24 h

miR-155 expression was significantly elevated

qPCR

Acute kidney injury

[114, 115]

Rat synovial fibroblast

LPS treatment

1 mg/L for 24 h

miR-155 expression was significantly higher in the LPS-treated group than in control group

qPCR

Rheumatoid arthritis

[116]

Human umbilical vein endothelial cells

LPS treatment

0.05, 0.1 and 1 μg/L for 24 h

The expression of miR-155 was enhanced by LPS in a dose dependent manner

qPCR

–

[117]

Mouse osteoblasts

LPS treatment

50 ng/mL for 0–48 h

miR-155 expression was upregulated in a time-dependent manner, reached a peak at 24 h

qPCR

Osteomyelitis

[118]

Mouse pre-osteoblast MC3T3-E1 cells

LPS treatment

100 and 200 ng/mL for 0–48 h

The level of miR-155 was significantly upregulated in a time-dependent manner upon LPS stimulation compared to the control

qPCR

Osteomyelitis

[119]

Mouse osteoclasts

LPS treatment

50 ng/mL for 24 and 48 h

The expression level of miR-155 was low in pre-OCs, whereas it was up-regulated upon LPS stimulation > 140-fold at 24 h and maintained it up to 48 h

qPCR

Inflammatory bone loss

[118]

Human breast cancer MCF-7 cells

LPS treatment

5 ng/mL for 6 and 12 h

The level of miR-155 expression was about threefold higher at 6 h after LPS stimulation

qPCR

Breast cancer

[120]

Human B-lymphoma BJAB cells

LPS treatment

5 μg/mL for 6 and 24 h

miR-155 levels were increased by ∼twofold after 6 h of LPS treatment and by ~ threefold at 24 h

qPCR

B-cell lymphoma

[121]

Treatment of BJAB cells with LPS for 6 h caused a significant increase in BIC mRNA levels and BIC mRNA remained elevated after 24 h treatment

Semi-quantitative RT-PCR

Mouse Insulinoma MIN6 Cells

LPS treatment

5, 20, or 50 ng/mL for 6 h

miR-155-5p expression was increased

qPCR

–

[122]

Human islet cells

LPS treatment

5 or 50 ng/mL for 6 h

miR-155-5p expression was increased

qPCR

–

[122]

Human bronchial epithelial 16HBE cells

LPS treatment

1 μg/mL for 6 h

miR-155 expression was induced by activation of TLR4 by LPS

qPCR

Chronic airway inflammatory diseases

[124]

Human intestinal myofibroblasts (IMF)

LPS treatment

1 μg/mL for 72 h

LPS increased miR-155 level following 72 h exposure in control-derived IMF and further upregulated miR-155 level in UC-derived IMF

qPCR

Ulcerative colitis

[131]

Human trophoblast HTR-8/SVneo cells

LPS treatment

0–800 ng/mL for 0.5–48 h

miR-155 was increased in a time- and dose-dependent manner and the highest level of miR-155 was observed at 24 h after 100 ng/mL LPS treatment

qPCR

Pre-eclampsia

[134]

Mouse brain tissues

Intraperitoneal injection of LPS

0.8 mg/kg single injection

miR-155 expression level was increased by LPS in comparison to the control mice

qPCR

Neuroinflammation

[125]

Mouse tibiae

Intraperitoneal injection of LPS

5 mg/kg once a week for 3 weeks

The expression of miR-155 in the tibiae of LPS-treated mice was approximately 3.4-fold higher than that in vehicle treated ones

qPCR

Inflammatory bone loss

[118]

Mouse myocardium tissues

Intraperitoneal injection of LPS

5 mg/kg single injection

miR-155 expression level was markedly elevated in the myocardium as early as 5 h post-LPS injection and at least persisted to 24 h

qPCR

Sepsis-induced myocardial dysfunction

[127]

Mouse liver tissues

Intraperitoneal injection of LPS

20 mg/kg single injection

At 6 h and 12 h after LPS administration, the level of miR-155 in liver tissues showed about sixfold or sevenfold increase

qPCR

Septic liver injury

[126]

Mouse kidney tissues

Intraperitoneal injection of LPS

20 mg/kg single injection

Renal cortex miR-155 was highly induced after LPS treatment

qPCR

Sepsis-associated kidney injury

[115]

Mouse prostatic tissues

Injection of LPS into the prostatic urinary tract

1 mg/mL single injection

miR-155 expression levels were significantly increased in psoriasis tissues compared with normal tissues

qPCR

Chronic prostatitis

[90]

Mouse lung tissues

Injection of LPS via the endotracheal intubation

1.25 mg/mL single injection

miR-155 expression levels in mouse lungs were significantly upregulated and reached a peak at around 6 h after LPS stimulation

qPCR

Acute lung injury

[128]

Rat lung tissues

Injection of LPS via the endotracheal intubation

10 mg/kg single injection

miR-155 was significantly overexpressed in LPS-induced acute lung injury

qPCR

Acute lung injury

[129]