KH-type splicing regulatory protein is regulated by nuclear factor-κB signaling to mediate innate immunity in Caco-2 cells infected by Salmonella enteritidis

Abstract

Salmonella enteritidis infection occurs in enterogenous diseases, such as gastroenteritis and parenteral focal infection, which often involve inflammation of intestinal epithelial cells. The nuclear factor kappa B (NF-κB) pathway participates in the innate immune response to many gram-negative pathogenic bacteria and initiates inflammation in epithelial cells. KH-type splicing regulatory protein (KSRP) is a multi-domain RNA-binding protein that recruits the exosome-containing mRNA degradation complex to mRNAs coding for inflammatory response factors. However, it remains unclear whether KSRP is regulated by NF-κB signaling pathway in response to S. enteritidis infection and affects the development of inflammation. Accordingly, in this study, we investigated the role of KSRP in mediating the response to S. enteritidis in Caco-2 cells. The data revealed that S. enteritidis infection decreased KSRP expression, which was suppressed by blocking the NF-κB pathway. Additionally, S. enteritidis infection significantly increased the expression of inducible nitric oxide synthase and cyclooxygenase-2. Overexpression of KSRP reduced the expression levels of inflammatory factors in Caco-2 cells. KSRP was regulated by the NF-κB signaling pathway and participated in mediating the innate immune response to S. enteritidis infection in Caco-2 cells, and KSRP acted as a negative regulator of inflammatory gene expression.

Sophy β-Glucan from the Black Yeast Aureobasidium pullulans Attenuates Salmonella-Induced Intestinal Epithelial Barrier Injury in Caco-2 Cell Monolayers via Exerting Anti-Oxidant and Anti-Inflammatory Properties

“…Pro-inflammatory cytokines such as TNF-α, interferon-γ, and IL-1β have been recognized to contribute to intestinal barrier dysfunction and exacerbate inflammatory responses, while anti-inflammatory cytokines (IL-10 and TGF-β) have been reported to be positively associated with intestinal barrier tissue repair during the course of inflammatory bowel disease [30]. In this study, the interaction of SE with intestinal epithelial cells induced obvious inflammatory responses in Caco-2 cells, as proven by up-regulating pro-inflammatory cytokines (IL-1β, IL-8, and TNF-α), which was consistent with the results of previous studies [31][32][33][34]. Interestingly, SE boosted IL-10 mRNA levels but decreased IL-10 protein levels.…”

RNA-binding protein KHSRP promotes tumor growth and metastasis in non-small cell lung cancer

“…To date, however, the molecular mechanisms by which KHSRP promotes lung cancer cell migration and invasion have not been elucidated. Previous studies have reported that activation of the KHSRP-mediated nuclear factor-κB, PI3K/AKT or p38 signaling pathway is closely associated with lung tumorigenesis and metastasis [16, 40, 41]. However, the detailed regulatory mechanisms remain unclear.…”

Immunomodulatory phytochemicals for chemoprevention

“…This effect could help in cell cycle arrest and initiate the programmed cell death by downregulating the NF-kB genes. [27][28][29][30][31][32][33][34][35][36][37][38][39][40][45][46][47][48][49][50] Curcumin reduces the iNOS i.e. inducible nitric oxide synthase which is concerned with oxidative stress and ROS generation through activation of neutrophils and macrophages.…”

“…47 Thus, Curcumin can stop cancer either by blocking the growth of cancer cells or by putting a halt on its invasion as shown inFigure 3. 47,48,[50][51][52][53][54][55][56] The structural activity relationship studies showed that substitution of ortho-methoxy group and hydrogenation of heptadiene group, both are responsible for scavenging of radicals 57,58 to give an antioxidant effect whereas less hydrogenation of the unsaturated diketone moiety and methoxylation of the molecules are highly responsible for the anti-inflammatory and anti-tumoral effect. 43 Further advanced studies showed that the presence of aromatic rings is important for cytotoxic and antiandrogenic activity along 59 with substitutions of 3´-dimethoxy and 4´dimethoxy and/or 3´-methoxy-4´-hydroxy substitutions on phenyl ring which will help in designing new Curcumin analogs.…”