scholarly journals Si Shen Wan Regulates Phospholipase Cγ-1 and PI3K/Akt Signal in Colonic Mucosa from Rats with Colitis

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Duan-yong Liu ◽  
Rong Xu ◽  
Min-fang Huang ◽  
Hong-yan Huang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Sulfonic Acid ◽  
Colonic Mucosa ◽  
Intestinal Epithelial Cells ◽  
Experimental Colitis ◽  
Mucosal Injury ◽  
Signal Pathway ◽  
Trinitrobenzene Sulfonic Acid ◽  
Intestinal Epithelial ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

The present study explored the feasible pathway of Si Shen Wan (SSW) in inhibiting apoptosis of intestinal epithelial cells (IECs) by observing activation of phospholipase Cγ-1 (PLC-γ1) and PI3K/Akt signal in colonic mucosa from rats with colitis. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in the Sprague-Dawley rats. After SSW was administrated for 7 days after TNBS infusion, western blot showed an increment in levels of PI3K, p-Akt, and IL-23 and a decrement in levels of PLC-γ1 and HSP70 in colonic mucosal injury induced by TNBS. Meanwhile, assessments by ELISA revealed an increment in concentrations of IL-2, IL-6, and IL-17 and a reduction in level of TGF-βafter TNBS challenge. Impressively, treatment with SSW for 7 days significantly attenuated the expressions of PI3K and p-Akt and the secretion of IL-2, IL-6, IL-17, and IL-23 and promoted the activation of PLC-γ1, HSP70, and TGF-β. Our previous studies had demonstrated that SSW restored colonic mucosal ulcers by inhibiting apoptosis of IECs. The present study demonstrated that the effect of SSW on inhibiting apoptosis of IECs was realized probably by activation of PLC-γ1 and suppression of PI3K/Akt signal pathway.

scholarly journals Effects of Curcumin on Bioavailability of Dioxin-Like Pollutants in Rats

2021 ◽  
Author(s):  
Delei Cai ◽  
Qing Chen ◽  
Jianlong Han ◽  
Yanhua Song ◽  
Zhen Meng ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Intestinal Epithelial Cells ◽  
Female Rats ◽  
Male Rats ◽  
Intestinal Epithelial ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Similar Chemical ◽  
Small Intestinal ◽  
Detoxification Mechanisms

Abstract In this study, we used Sprague–Dawley rats to observe the intervention effects of curcumin on bioavailability of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (DL-PCBs). We reported the bioavailability of tetra- to hexa-chlorinated PCDD/Fs rose gradually, while that of hepta- and octa-chlorinated PCDD/Fs declined, and no obvious change was found in the bioavailability of DL-PCBs. Curcumin markedly reduced the toxic equivalent (TEQ) of PCDD/Fs in rats, illustrating it might competitively inhibit absorption of PCDD/Fs in small intestinal epithelial cells due to the similar chemical structure (diphenyl) between curcumin and PCDD/Fs. Moreover, curcumin was capable of lowering the TEQ of DL-PCBs in the liver of male rats, but caused no changes in female rats. In conclusion, the prominent decline in the bioavailability of PCDD/Fs and DL-PCBs induced by curcumin may serve as one of the detoxification mechanisms of curcumin for these pollutants.

scholarly journals Huang Qi Jian Zhong Pellet Attenuates TNBS-Induced Colitis in Rats via Mechanisms Involving Improvement of Energy Metabolism

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Duan-Yong Liu ◽  
Chun-Shui Pan ◽  
Yu-Ying Liu ◽  
Xiao-Hong Wei ◽  
Chang-Man Zhou ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Inflammatory Responses ◽  
Mucosal Injury ◽  
Underlying Mechanism ◽  
Trinitrobenzene Sulfonic Acid ◽  
Sprague Dawley ◽  
Colonic Injury ◽  
Sprague Dawley Rats ◽  
Microcirculatory Disturbances

Huang Qi Jian Zhong Pellet (HQJZ) is a famous Chinese medicine formula for treatment of various gastrointestinal tract diseases. This study investigated the role of HQJZ in 2,4,6-trinitrobenzene sulfonic acid- (TNBS-) induced colitis and its underlying mechanism. Colonic mucosal injury was induced by TNBS in the Sprague-Dawley rats. In the HQJZ treatment group, HQJZ was administered (2 g/kg) for 14 days starting from day 1 after TNBS infusion. Colonic mucosal injury occurred obviously 1 day after TNBS challenge and did not recover distinctively until day 15, including an increase in macro- and microscopic scores, a colonic weight index, a decrease in colonic length, a number of functional capillaries, and blood flow. Inverted intravital microscopy and ELISA showed colonic microcirculatory disturbances and inflammatory responses after TNBS stimulation, respectively. TNBS decreased occludin, RhoA, and ROCK-I, while increasing Rac-1, PAK-1, and phosphorylated myosin light chain. In addition, ATP content and ATP5D expression in colonic mucosa decreased after TNBS challenge. Impressively, treatment with HQJZ significantly attenuated all of the alterations evoked by TNBS, promoting the recovery of colonic injury. The present study demonstrated HQJZ as a multitargeting management for colonic mucosal injury, which set in motion mechanisms involving improvement of energy metabolism.

scholarly journals Expression of TNFAIP3 in intestinal epithelial cells protects from DSS- but not TNBS-induced colitis

2012 ◽  
Vol 303 (2) ◽  
pp. G220-G227 ◽  
Author(s):  
Lesley Rhee ◽  
Stephen F. Murphy ◽  
Lauren E. Kolodziej ◽  
Wesley A. Grimm ◽  
Christopher R. Weber ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Sulfonic Acid ◽  
Feedback Loop ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Lumen ◽  
Mucosal Inflammation ◽  
Trinitrobenzene Sulfonic Acid ◽  
Intestinal Epithelial ◽  
Wild Type

Intestinal epithelial cells (IEC) maintain gastrointestinal homeostasis by providing a physical and functional barrier between the intestinal lumen and underlying mucosal immune system. The activation of NF-κB and prevention of apoptosis in IEC are required to maintain the intestinal barrier and prevent colitis. How NF-κB activation in IEC prevents colitis is not fully understood. TNFα-induced protein 3 (TNFAIP3) is a NF-κB-induced gene that acts in a negative-feedback loop to inhibit NF-κB activation and also to inhibit apoptosis; therefore, we investigated whether TNFAIP3 expression in the intestinal epithelium impacts susceptibility of mice to colitis. Transgenic mice expressing TNFAIP3 in IEC (villin-TNFAIP3 Tg mice) were exposed to dextran sodium sulfate (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS), and the severity and characteristics of mucosal inflammation and barrier function were compared with wild-type mice. Villin-TNFAIP3 Tg mice were protected from DSS-induced colitis and displayed reduced production of NF-κB-dependent inflammatory cytokines. Villin-TNFAIP3 Tg mice were also protected from DSS-induced increases in intestinal permeability and induction of IEC death. Villin-TNFAIP3 Tg mice were not protected from colitis induced by TNBS. These results indicate that TNFAIP3 expression in IEC prevents colitis involving DSS-induced IEC death, but not colitis driven by T cell-mediated inflammation. As TNFAIP3 inhibits NF-κB activation and IEC death, expression of TNFAIP3 in IEC may provide an avenue to inhibit IEC NF-κB activation without inducing IEC death and inflammation.

The cartilage degeneration in a growing rat experimental model of developmental trochlear dysplasia is associated with activation of PI3K/AKT signal pathway

2020 ◽  
Author(s):  
Wei Lin ◽  
Yike Dai ◽  
Jinghui Niu ◽  
Chongyi Fan ◽  
Xunkai Feng ◽  
...  
Keyword(s):  
Trochlear Dysplasia ◽  
Cartilage Degeneration ◽  
Signal Pathway ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Growing Rat ◽  
Polymerase Chain ◽  
Underlying Mechanisms ◽  
Experimental Group

Abstract Background As one of the lower extremity deformities in human, trochlear dysplasia is a commonly encountered disease. However, the molecular mechanism of cartilage degeneration in trochlear dysplasia is indefinite yet. It was apparent to all that PI3K/AKT signal pathway is extremely significant in regulating the pathophysiological process of cartilage degeneration. The purpose of this research is to discuss the correlation between PI3K/AKT signal pathway and trochlear dysplasia cartilage degeneration. Materials and methods 120 female Sprague-Dawley rats at 4 weeks of age were separate into control group and experimental group randomly. The distal femurs were isolated from the experimental and unsurgeried control group at the point of the 4, 8, 12 weeks, correspondingly. Micro-CT and histological examination were carried out to investigate the anatomical structure and cartilage changes of the trochlear. Subsequently, the expression of PI3K/AKT, TGFβ1 and ADAMTS-4 in cartilage were investigated by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). Results In the experimental group, the trochlear dysplasia model was successfully established at 8 weeks after surgery. Moreover, the cartilage degeneration was found from 8 weeks, with continued higher protein and mRNA expression of PI3K/AKT, TGFβ1 and ADAMTS-4 compared with the control group. Conclusions This research suggested that patellar instability may lead to trochlear dysplasia in growing rats. Moreover, trochlear dysplasia was probably one of the causes of patellofemoral osteoarthritis and the cartilage degeneration in trochlear dysplasia might be associate with activation of PI3K/AKT signal pathway. However, more research was required to clarify the underlying mechanisms.

scholarly journals RETRACTED ARTICLE:Deficiency in intestinal epithelial Reg4 ameliorates intestinal inflammation and alters the colonic bacterial composition

2019 ◽  
Vol 12 (4) ◽  
pp. 919-929 ◽  
Author(s):  
Yongtao Xiao ◽  
Ying Lu ◽  
Ying Wang ◽  
Weihui Yan ◽  
Wei Cai
Keyword(s):  
Intestinal Inflammation ◽  
Elevated Serum ◽  
Intestinal Failure ◽  
Experimental Colitis ◽  
Mucosal Injury ◽  
Intestinal Epithelial ◽  
Bacterial Composition ◽  
Novel Target

AbstractThe regenerating islet-derived family member 4 (Reg4) in the gastrointestinal tract is up-regulated during intestinal inflammation. However, the physiological function of Reg4 in the inflammation is largely unknown. In the current study, the functional roles and involved mechanisms of intestinal epithelial Reg4 in intestinal inflammation were studied in healthy and inflamed states using human intestinal specimens, an intestinal conditional Reg4 knockout mouse (Reg4ΔIEC) model and dextran sulfate sodium (DSS)-induced colitis model. We showed that the elevated serum Reg4 in pediatric intestinal failure (IF) patients were positively correlated with the serum concentrations of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In inflamed intestine of IF patients, the crypt base Reg4 protein was increased and highly expressed towards the luminal face. The Reg4 was indicated as a novel target of activating transcription factor 2 (ATF2) that enhanced Reg4 expression during the intestinal inflammation. In vivo, the DSS-induced colitis was significantly ameliorated in Reg4ΔIEC mice. Reg4ΔIEC mice altered the colonic bacterial composition and reduced the bacteria adhere to the colonic epithelium. In vitro, Reg4 was showed to promote the growth of colonic organoids, and that this occurs through a mechanism involving activation of signal transducer and activator of transcription 3 (STAT3). In conclusion, our findings demonstrated intestinal-epithelial Reg4 deficiency protects against experimental colitis and mucosal injury via a mechanism involving alteration of bacterial homeostasis and STAT3 activation.

scholarly journals Treatment of Experimental (Trinitrobenzene Sulfonic Acid) Colitis by Intranasal Administration of Transforming Growth Factor (Tgf)-β1 Plasmid

2000 ◽  
Vol 192 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Atsushi Kitani ◽  
Ivan J. Fuss ◽  
Kazuhiko Nakamura ◽  
Owen M. Schwartz ◽  
Takashi Usui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sulfonic Acid ◽  
Transforming Growth Factor ◽  
Intraperitoneal Administration ◽  
Experimental Colitis ◽  
Inhibitory Effect ◽  
Transforming Growth Factor Β1 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Ifn Γ ◽  
Tgf Β1

In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor β1 (pCMV-TGF-β1) prevents the development of T helper cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-β1 protein does not have this effect. Intranasal pCMV-TGF-β1 administration leads to the expression of TGF-β1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-β1–producing T cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-γ production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor β2 (IL-12Rβ2) chain expression. Coadministration of anti–IL-10 at the time of pCMV-TGF-β1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-γ secretion. However, anti–IL-10 leads to increased tumor necrosis factor α production, especially in established colitis. Taken together, these studies show that TGF-β1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rβ2 chain expression. In addition, TGF-β1 may also have an inhibitory effect on IFN-γ transcription.

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