scholarly journals Bacteroides fragilis Enterotoxin Induces Human β-Defensin-2 Expression in Intestinal Epithelial Cells via a Mitogen-Activated Protein Kinase/IκB Kinase/NF-κB-Dependent Pathway

2010 ◽  
Vol 78 (5) ◽  
pp. 2024-2033 ◽  
Author(s):  
Young Mee Yoon ◽  
Jin Young Lee ◽  
Doyoung Yoo ◽  
Young-Suk Sim ◽  
Young-Jeon Kim ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Bacteroides Fragilis ◽  
Mitogen Activated Protein Kinase ◽  
Mucosal Inflammation ◽  
Intestinal Epithelial ◽  
Iκb Kinase ◽  
Mitogen Activated Protein ◽  
Spontaneous Disappearance

ABSTRACT Enterotoxigenic Bacteroides fragilis (ETBF) produces an approximately 20-kDa heat-labile enterotoxin (BFT) that plays an essential role in mucosal inflammation. Although spontaneous disappearance of ETBF infection is common, little information is available on regulated expression of antibacterial factors in response to BFT stimulation. This study investigates the role of BFT in human β-defensin 2 (hBD-2) induction from intestinal epithelial cells. Stimulation of HT-29 and Caco-2 intestinal epithelial cell lines with BFT resulted in the induction of hBD-2. Activation of a reporter gene for hBD-2 was dependent on the presence of NF-κB binding sites. In contrast, suppression of AP-1 did not affect hBD-2 expression in BFT-stimulated cells. Inhibition of p38 mitogen-activated protein kinase (MAPK) using SB203580 and small interfering RNA (siRNA) transfection resulted in a significant reduction in BFT-induced IκB kinase (IKK)/NF-κB activation and hBD-2 expression. Our results suggest that a pathway including p38 MAPK, IKK, and NF-κB activation is required for hBD-2 induction in intestinal epithelial cells exposed to BFT, and may be involved in the host defense following infection with ETBF.

scholarly journals Bacteroides fragilis Enterotoxin Upregulates Heme Oxygenase-1 in Intestinal Epithelial Cells via a Mitogen-Activated Protein Kinase- and NF-κB-Dependent Pathway, Leading to Modulation of Apoptosis

2016 ◽  
Vol 84 (9) ◽  
pp. 2541-2554 ◽  
Author(s):  
Su Hyuk Ko ◽  
Da Jeong Rho ◽  
Jong Ik Jeon ◽  
Young-Jeon Kim ◽  
Hyun Ae Woo ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Heme Oxygenase ◽  
Inflammatory Responses ◽  
Intestinal Epithelial Cells ◽  
Bacteroides Fragilis ◽  
Heme Oxygenase 1 ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Iκb Kinase ◽  
Mitogen Activated Protein

TheBacteroides fragilisenterotoxin (BFT), a virulence factor of enterotoxigenicB. fragilis(ETBF), interacts with intestinal epithelial cells and can provoke signals that induce mucosal inflammation. Although expression of heme oxygenase-1 (HO-1) is associated with regulation of inflammatory responses, little is known about HO-1 induction in ETBF infection. This study was conducted to investigate the effect of BFT on HO-1 expression in intestinal epithelial cells. Stimulation of intestinal epithelial cells with BFT resulted in upregulated expression of HO-1. BFT activated transcription factors such as NF-κB, AP-1, and Nrf2 in intestinal epithelial cells. Upregulation of HO-1 in intestinal epithelial cells was dependent on activated IκB kinase (IKK)–NF-κB signals. However, suppression of Nrf2 or AP-1 signals in intestinal epithelial cells did not result in significant attenuation of BFT-induced HO-1 expression. HO-1 induction via IKK–NF-κB in intestinal epithelial cells was regulated by p38 mitogen-activated protein kinases (MAPKs). Furthermore, suppression of HO-1 activity led to increased apoptosis in BFT-stimulated epithelial cells. These results suggest that a signaling pathway involving p38 MAPK–IKK–NF-κB in intestinal epithelial cells is required for HO-1 induction during exposure to BFT. Following this induction, increased HO-1 expression may regulate the apoptotic process in responses to BFT stimulation.

Leukotriene D4 activates MAPK through a Ras-independent but PKCϵ-dependent pathway in intestinal epithelial cells

2002 ◽  
Vol 115 (9) ◽  
pp. 1883-1893
Author(s):  
Sailaja Paruchuri ◽  
Bengt Hallberg ◽  
Maria Juhas ◽  
Christer Larsson ◽  
Anita Sjölander
Keyword(s):  
Protein Kinase ◽  
Epithelial Cells ◽  
Proliferative Response ◽  
Egf Receptor ◽  
Intestinal Epithelial Cells ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Intestinal Epithelial ◽  
Leukotriene D4 ◽  
Mitogen Activated Protein

We have recently shown that leukotriene D4 (LTD4)increases cell survival in intestinal epithelial cells. Here we report and explore the complementary finding that LTD4 also enhances proliferation in these cells. This proliferative response was approximately half of that induced by epidermal growth factor (EGF) and its required activation of protein kinase C (PKC), Ras and the mitogen-activated protein kinase (MAPK) Erk-1/2. EGF also activated Erk-1/2 in these cells; however the EGF-receptor inhibitor PD153035 did not affect the LTD4-induced activation of Erk-1/2. In addition, LTD4 did not induce phosphorylation of the EGF receptor, nor did pertussis toxin (PTX) block EGF-induced activation of Erk-1/2, thus refuting a possible crosstalk between the receptors. Furthermore, LTD4-induced, but not EGF-induced,activation of Erk-1/2 was sensitive to PTX, PKC inhibitors and downregulation of PKCϵ. A definite role for PKCϵ in LTD4-induced stimulation of Erk-1/2 was documented by the inability of LTD4 to activate Erk-1/2 in cells transfected with either the regulatory domain of PKCϵ (an isoform specific dominant-negative inhibitor) or a kinase-dead PKCϵ. Although Ras and Raf-1 were both transiently activated by LTD4, only Raf-1 activation was abolished by abrogation of the PKC signal. Furthermore, the LTD4-induced activation of Erk-1/2 was unaffected by transfection with dominant-negative N17 Ras but blocked by transfection with kinase-dead Raf-1. Consequently, LTD4 regulates the proliferative response by a distinct Ras-independent, PKCϵ-dependent activation of Erk-1/2 and a parallel Ras-dependent signaling pathway.

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