scholarly journals NLRP3-Dependent and -Independent Processing of Interleukin (IL)-1β in Active Ulcerative Colitis

2018 ◽  
Vol 20 (1) ◽  
pp. 57 ◽  
Author(s):  
Nicole Ranson ◽  
Mark Veldhuis ◽  
Brent Mitchell ◽  
Scott Fanning ◽  
Anthony Cook ◽  
...  

A contributing factor in the development of ulcerative colitis (UC) and Crohn’s disease (CD) is the disruption of innate and adaptive signaling pathways due to aberrant cytokine production. The cytokine, interleukin (IL)-1β, is highly inflammatory and its production is tightly regulated through transcriptional control and both inflammasome-dependent and inflammasome- independent proteolytic cleavage. In this study, qRT-PCR, immunohistochemistry, immunofluorescence confocal microscopy were used to (1) assess the mRNA expression of NLRP3, IL-1β, CASP1 and ASC in paired biopsies from UC and CD patient, and (2) the colonic localization and spatial relationship of NLRP3 and IL-1β in active and quiescent disease. NLRP3 and IL-1β were found to be upregulated in active UC and CD. During active disease, IL-1β was localized to the infiltrate of lamina propria immune cells, which contrasts with the near-exclusive epithelial cell layer expression during non-inflammatory conditions. In active disease, NLRP3 was consistently expressed within the neutrophils and other immune cells of the lamina propria and absent from the epithelial cell layer. The disparity in spatial localization of IL-1β and NLRP3, observed only in active UC, which is characterized by a neutrophil-dominated lamina propria cell population, implies inflammasome-independent processing of IL-1β. Consistent with other acute inflammatory conditions, these results suggest that blocking both caspase-1 and neutrophil-derived serine proteases may provide an additional therapeutic option for treating active UC.

2006 ◽  
Vol 175 (4S) ◽  
pp. 469-469
Author(s):  
W. Steve Ammons ◽  
Tatyana Lukoyanova ◽  
Amber Durnal ◽  
Geoffrey Del Rosario ◽  
Alan Colowick

2015 ◽  
Vol 166 (4) ◽  
pp. 291-296 ◽  
Author(s):  
Katharina Gangl ◽  
Eva E. Waltl ◽  
Helga Vetr ◽  
Clarissa R. Cabauatan ◽  
Katarzyna Niespodziana ◽  
...  

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Ang Su ◽  
Jie Tong ◽  
Yuguang Fu ◽  
Sandy Müller ◽  
Yenehiwot Berhanu Weldearegay ◽  
...  

AbstractPasteurella (P.) multocida is a zoonotic pathogen, which is able to cause respiratory disorder in different hosts. In cattle, P. multocida is an important microorganism involved in the bovine respiratory disease complex (BRDC) with a huge economic impact. We applied air–liquid interface (ALI) cultures of well-differentiated bovine airway epithelial cells to analyze the interaction of P. multocida with its host target cells. The bacterial pathogen grew readily on the ALI cultures. Infection resulted in a substantial loss of ciliated cells. Nevertheless, the epithelial cell layer maintained its barrier function as indicated by the transepithelial electrical resistance and the inability of dextran to get from the apical to the basolateral compartment via the paracellular route. Analysis by confocal immunofluorescence microscopy confirmed the intactness of the epithelial cell layer though it was not as thick as the uninfected control cells. Finally, we chose the bacterial neuraminidase to show that our infection model is a sustainable tool to analyze virulence factors of P. multocida. Furthermore, we provide an explanation, why this microorganism usually is a commensal and becomes pathogenic only in combination with other factors such as co-infecting microorganisms.


2020 ◽  
Vol 27 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Ritika Rampal ◽  
Nahidul Wari ◽  
Amit Kumar Singh ◽  
Ujjwalkumar Das ◽  
Sawan Bopanna ◽  
...  

Abstract Background All-trans retinoic acid (RA) plays a crucial role in promoting Foxp3+ Treg generation while reciprocally inhibiting Th1/Th17 generation. Our previous research highlighted that in the face of inflammatory conditions, RA plays a contrary role where it aggravates intestinal inflammation by promoting interferon (IFN) γ and interleukin (IL)-17 differentiation in vitro. Methods In this study we translated our in vitro results into a clinical setting where we estimated mucosal and serum RA levels along with the immunophenotypic profile (IL-17, IFNγ, Foxp3, IL-10) in adaptive (CD4, CD8) and innate-like T cells (mucosal associated invariant T cells and γδ T cells) in patients with ulcerative colitis in remission or with active inflammation. Results This is the first study to estimate RA levels in the human gut and shows that patients with active disease had increased mucosal RA levels as compared with patients in remission (4.0 vs 2.5 ng/mL; P < 0.01) and control patients (3.4 vs 0.8 ng/mL; P < 0.0001). This effect was accompanied by significantly elevated IL-17 and IFNγ in tissue CD4+, CD8+, mucosal associated invariant T+ cells, and γδ + T cells. Moreover, the raised RA levels in patients with active disease showed a positive correlation with proinflammatory cytokines (IL-17, IFNγ) and a negative correlation with IL-10. We also found that RA negatively correlated with IL-9, thereby reinstating our previous finding that RA inhibits Th9 differentiation. Conclusions These data confirm our previous in vitro results that in the presence of inflammation, RA plays a crucial role in maintaining gut inflammation by upregulating proinflammatory markers.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hau-Wen Li ◽  
Chih Chen ◽  
Wei-Lun Kuo ◽  
Chien-Ju Lin ◽  
Ching-Fong Chang ◽  
...  

AbstractThe accessory nidamental gland (ANG) is a female reproductive organ found in most squid and cuttlefish that contains a consortium of bacteria. These symbiotic bacteria are transmitted from the marine environment and selected by the host through an unknown mechanism. In animals, a common antimicrobial mechanism of innate immunity is iron sequestration, which is based on the development of transferrin (TF)-like proteins. To understand this mechanism of host-microbe interaction, we attempted to characterize the role of transferrin in bigfin reef squid (Sepioteuthis lessoniana) during bacterial transmission. qPCR analysis showed that Tf was exclusively expressed in the outer layer of ANG,and this was confirmed by in situ hybridization, which showed that Tf was localized in the outer epithelial cell layer of the ANG. Western blot analysis indicated that TF is a soluble glycoprotein. Immunohistochemical staining also showed that TF is localized in the outer epithelial cell layer of the ANG and that it is mainly expressed in the outer layer during ANG growth. These results suggest that robust Tf mRNA and TF protein expression in the outer layer of the ANG plays an important role in microbe selection by the host during bacterial transmission.


2018 ◽  
Vol 9 (8) ◽  
pp. 4164-4172 ◽  
Author(s):  
Mensiena B. G. Kiewiet ◽  
Martín I. González Rodríguez ◽  
Renske Dekkers ◽  
Marjan Gros ◽  
Laurien H. Ulfman ◽  
...  

A soy hydrolysate protects the epithelial cell layer from an increase in permeability in a barrier disruptor specific manner.


1987 ◽  
Vol 36 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Masao KOTO ◽  
Masao MIWA ◽  
Ko-ichiro TSUJI ◽  
Michio OKAMOTO ◽  
Jiro ADACHI

2015 ◽  
Vol 7 (10) ◽  
pp. 1253-1264 ◽  
Author(s):  
Adrian R. Noppe ◽  
Anthony P. Roberts ◽  
Alpha S. Yap ◽  
Guillermo A. Gomez ◽  
Zoltan Neufeld

We use a two-dimensional cellular Potts model to represent the behavior of an epithelial cell layer and describe its dynamics in response to a microscopic wound.


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