The pathogenesis of inflammatory bowel disease (IBD) is believed to be associated with the abnormal expression of inflammatory factors. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor, which can suppress the inflammatory response and attenuate experimental colitis. However, the detailed mechanism underlying the effects of AhR remains unclear. The present study investigated the role of AhR in the pathogenesis of IBD. Colitis was induced in mice by administration of 3% dextran sulphate sodium (DSS) for 7 days. The mice were also administered injections of the AhR agonist, 6-formylindolo(3,2-b)carbazole (FICZ), starting 2 days after the first administration of DSS. Furthermore, LoVo cells were treated with lipopolysaccharide (LPS) in the presence or absence of FICZ for 8 h. The protein expression levels of AhR, cytochrome P450 1A1 (CYP1A1) and tristetraprolin (TTP) were assessed by western blotting and immunofluorescence, whereas mRNA expression levels were assessed by reverse transcription-quantitative polymerase chain reaction. The results indicated that injection of mice with FICZ significantly attenuated DSS-induced colitis; in addition, the expression levels of inflammatory cytokines were markedly downregulated. Conversely, the expression levels of AhR and TTP were upregulated. In addition, mice in the AhR-knockout + DSS group exhibited elevated inflammatory cytokine production and developed more severe colitis. In LoVo cells, incubation with FICZ decreased the expression levels of inflammatory cytokines, whereas AhR and TTP expression was increased. In addition, the levels of phosphorylated-mitogen-activated protein kinase-activated protein kinase 2 (p-MK2) were decreased. These results suggested that AhR deficiency resulted in increased susceptibility to colitis, whereas activation of AhR by FICZ could ameliorate DSS-induced colitis via the MK2/p-MK2/TTP pathway.

AhR activation can ameliorate epithelial barrier dysfunction induced by IO through the suppression of MLCK-pMLC signaling, suggesting that AhR agonist may be a suitable means of addressing this condition.

Herein, high‐performance enhancement‐mode (E‐mode) β‐Ga2O3 metal‐oxide‐semiconductor field‐effect transistors (MOSFETs) are achieved on Si‐doped homoepitaxial films. Oxygen annealing (OA) treatment under the gate region is used to effectively exhaust the channel electron, resulting in the normally off operation of the device. The threshold voltage, defined as that at the drain current of 0.1 mA mm−1, for the fabricated device is extracted to be 4.1 V. Moreover, double source‐connected field plates are used to suppress the peak electric fields in both Ga2O3 channel and SiNx passivation layer. The fabricated β‐Ga2O3 MOSFETs with gate‐to‐drain distance (Lgd) of 17 μm exhibit a record high breakdown voltage over 3000 V. It is shown that the OA treatment is a new way to obtain high‐performance E‐mode β‐Ga2O3 power MOSFETs.

TLR2 signaling is related to colitis and involved in regulation of innate immunity in the intestinal tract, but the mechanisms remain unclear. The aim of this study is to investigate how TLR2 affects differentiation of intraepithelial lymphocytes (IELs) and regulates the susceptibility of colitis. IELs were isolated from the small intestine and colon of mice, respectively. The IEL phenotype, activation, and apoptosis were examined using flow cytometry and RT-PCR. IL-15 expression and IEL location were detected through immunohistochemistry. The experimental colitis was induced by administration of dextran sulfate sodium (DSS). We found that the numbers of CD8αα +, CD8αβ +, and TCRγδ + IELs were significantly decreased in TLR2-deficient mice and the residual IELs displayed reduced activation and proliferation and increased apoptosis, accompanied with impaired IL-15 expression by intestinal epithelial cells (IECs). Further study showed that TLR2 signaling maintained the expression of IL-15 in IEC via NF-κB activation. Moreover, TLR2-deficient mice were found to be more susceptible to DSS-induced colitis as shown by the increased severity of colitis. Our results demonstrate that IECs contribute to the maintenance of IELs at least partly via TLR2-dependent IL-15 production, which provides a clue that may link IECs to innate immune protection of the host via IELs.

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Some ingredients in foods can activate the aryl hydrocarbon receptor (AhR) and arrest cell proliferation. In this study, we hypothesized that 6-formylindolo [3, 2-b] carbazole (FICZ) arrests the cell cycle in LoVo cells (a colon cancer line) through the AhR. The AhR agonist FICZ and the AhR antagonist CH223191 were used to treat LoVo cells. Real-time PCR and Western blot analyses were performed to detect the expression of the AhR, CYP1A1, CDK4, cyclinD1, cyclin E, CDK2, P27, and pRb. The distribution and activation of the AhR were detected with immunofluorescence. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometric analysis were performed to measure cell viability, cell cycle stage, and apoptosis. Our results show that FICZ inhibited LoVo cell proliferation by inducing G1 cell cycle arrest but had no effect on epithelial apoptosis. Further analysis found that FICZ downregulated cyclinD1 and upregulated p27 expression to arrest Rb phosphorylation. The downregulation of cyclinD1 and upregulation of p27 were abolished by co-treatment with CH223191. We conclude that the AhR, when activated by FICZ (an endogenous AhR ligand), can arrest the cell cycle and block LoVo cell proliferation.

Our study suggests that KGF, AhR, and CYP1A1 are overexpressed in colorectal cancer tissues. Moreover, we reveal a new mechanism by which KGF promotes cell proliferation through the AhR-cyclin D1 pathway in colon cancer cells.

The pathogenesis of intestinal ischemia/reperfusion (I/R) is associated with dysregulation of the intestinal immune system. The aryl hydrocarbon receptor (AhR), a receptor expressed in gamma-delta (γδ) intraepithelial lymphocytes (IELs), is thought to regulate inflammation in the bowel. γδIELs are a key immunologic compartment with a capacity to modulate immune responses. In the present study, the function of the AhR in γδIELs in a mouse model of intestinal I/R injury was investigated to determine whether the AhR attenuates intestinal injury induced by intestinal I/R. Mice were assigned to three groups: sham, I/R and I/R+6-formylindolo(3,2-b) carbazole (FICZ). The sham group received no ischemia treatment, whereas the I/R and I/R+FICZ groups underwent upper mesenteric vessel ischemia for 30 min. The I/R group was injected intraperitoneally with 0.3 ml saline and the I/R+FICZ group was administered 1 µg of FICZ before a subsequent 6 h reperfusion. Then, the mice were sacrificed and the entire small intestinal tissues were collected for histologic examination. The phenotype and apoptosis of γδIELs and activation of CD4 + and CD8 + IELs were examined using flow cytometry. The cytokine mRNA and anti-apoptosis gene expression in IELs were measured by qPCR. FICZ increased the γδIEL population and anti-apoptosis genes in the γδIELs. FICZ reduced the percentage of activated CD4 + and CD8 + subpopulations and the expression of pro-inflammatory mediator genes in IELs. FICZ inhibited inflammation in the gastrointestinal tract of mice with I/R injury. These results suggest that the AhR plays an important role in protecting the small intestine from I/R and increasing the γδIEL population by decreasing apoptosis of γδIELs.