Increased expression of chemokine receptor CCR3 and its ligands in ulcerative colitis: the role of colonic epithelial cells in in vitro studies

Reactive oxygen species (ROS) are released into the alveolar space and contribute to alveolar epithelial damage in patients with acute lung injury. However, the role of ROS in alveolar repair is not known. We studied the effect of ROS in our in vitro wound healing model using either human A549 alveolar epithelial cells or primary distal lung epithelial cells. We found that H2O2 inhibited alveolar epithelial repair in a concentration-dependent manner. At similar concentrations, H2O2 also induced apoptosis, an effect seen particularly at the edge of the wound, leading us to hypothesize that apoptosis contributes to H2O2-induced inhibition of wound repair. To learn the role of apoptosis, we blocked caspases with the pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (zVAD). In the presence of H2O2, zVAD inhibited apoptosis, particularly at the wound edge and, most importantly, maintained alveolar epithelial wound repair. In H2O2-exposed cells, zVAD also maintained cell viability as judged by improved cell spreading and/or migration at the wound edge and by a more normal mitochondrial potential difference compared with cells not treated with zVAD. In conclusion, H2O2 inhibits alveolar epithelial wound repair in large part by induction of apoptosis. Inhibition of apoptosis can maintain wound repair and cell viability in the face of ROS. Inhibiting apoptosis may be a promising new approach to improve repair of the alveolar epithelium in patients with acute lung injury.

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Identification of a microRNA signature in renal fibrosis: role of miR-21

AJP Renal Physiology ◽

10.1152/ajprenal.00273.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. F793-F801 ◽

Cited By ~ 169

Author(s):

Abolfazl Zarjou ◽

Shanzhong Yang ◽

Edward Abraham ◽

Anupam Agarwal ◽

Gang Liu

Keyword(s):

Epithelial Cells ◽

Renal Fibrosis ◽

Transforming Growth Factor ◽

Response To Treatment ◽

Tubular Epithelial Cells ◽

Altered Expression ◽

Tnf Α ◽

Tgf Β1

Renal fibrosis is a final stage of many forms of kidney disease and leads to impairment of kidney function. The molecular pathogenesis of renal fibrosis is currently not well-understood. microRNAs (miRNAs) are important players in initiation and progression of many pathologic processes including diabetes, cancer, and cardiovascular disease. However, the role of miRNAs in kidney injury and repair is not well-characterized. In the present study, we found a unique miRNA signature associated with unilateral ureteral obstruction (UUO)-induced renal fibrosis. We found altered expression in UUO kidneys of miRNAs that have been shown to be responsive to stimulation by transforming growth factor (TGF)-β1 or TNF-α. Among these miRNAs, miR-21 demonstrated the greatest increase in UUO kidneys. The enhanced expression of miR-21 was located mainly in distal tubular epithelial cells. miR-21 expression was upregulated in response to treatment with TGF-β1 or TNF-α in human renal tubular epithelial cells in vitro. Furthermore, we found that blocking miR-21 in vivo attenuated UUO-induced renal fibrosis, presumably through diminishing the expression of profibrotic proteins and reducing infiltration of inflammatory macrophages in UUO kidneys. Our data suggest that targeting specific miRNAs could be a novel therapeutic approach to treat renal fibrosis.

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C3 Promotes Clearance of Klebsiella pneumoniae by A549 Epithelial Cells

Infection and Immunity ◽

10.1128/iai.72.3.1767-1774.2004 ◽

2004 ◽

Vol 72 (3) ◽

pp. 1767-1774 ◽

Cited By ~ 26

Author(s):

Beatriz de Astorza ◽

Guadalupe Cortés ◽

Catalina Crespí ◽

Carles Saus ◽

José María Rojo ◽

...

Keyword(s):

Epithelial Cells ◽

Klebsiella Pneumoniae ◽

Alveolar Epithelial Cells ◽

Clinical Isolates ◽

Complement Components ◽

Innate Defense ◽

Alveolar Epithelial

ABSTRACT The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense.

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Cellular Samurai: katanin and the severing of microtubules

Journal of Cell Science ◽

10.1242/jcs.113.16.2821 ◽

2000 ◽

Vol 113 (16) ◽

pp. 2821-2827 ◽

Cited By ~ 5

Author(s):

L. Quarmby

Keyword(s):

Epithelial Cells ◽

Essential Role ◽

Aaa Atpase ◽

C Elegans ◽

Microtubule Severing ◽

Biochemical Studies ◽

New Evidence

Recent biochemical studies of the AAA ATPase, katanin, provide a foundation for understanding how microtubules might be severed along their length. These in vitro studies are complemented by a series of recent reports of direct in vivo observation of microtubule breakage, which indicate that the in vitro phenomenon of catalysed microtubule severing is likely to be physiological. There is also new evidence that microtubule severing by katanin is important for the production of non-centrosomal microtubules in cells such as neurons and epithelial cells. Although it has been difficult to establish the role of katanin in mitosis, new genetic evidence indicates that a katanin-like protein, MEI-1, plays an essential role in meiosis in C. elegans. Finally, new proteins involved in the severing of axonemal microtubules have been discovered in the deflagellation system of Chlamydomonas.

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CD39/CD73/A2a Adenosine Metabolic Pathway: Targets for Moxibustion in Treating DSS-Induced Ulcerative Colitis

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500300 ◽

2021 ◽

Vol 49 (03) ◽

pp. 661-676

Author(s):

Yuanbing Zhu ◽

Zhiqi Zhuang ◽

Qiaofeng Wu ◽

Sirui Lin ◽

Na Zhao ◽

...

Keyword(s):

Ulcerative Colitis ◽

Dextran Sulfate ◽

Dextran Sulfate Sodium ◽

Animal Experiments ◽

Treg Cells ◽

Colonic Tissue ◽

Colonic Epithelial Cells ◽

A2a Receptor ◽

Draining Lymph Nodes

Ulcerative Colitis (UC) is a chronic inflammation disease, and the incidence of UC is increasing recently. Both clinical trials and animal experiments show that moxibustion is a complementary and alternative treatment for UC. Previous studies showed that moxibustion can improve UC by regulating the balance of Tregs and Th17 (Sun et al., 2017). Treg cells is one subset of CD4[Formula: see text] T cells that exert the immunosuppressive function. CD39 and CD73, expressed on the surface of Tregs, hydrolyze ATP to AMP and are further involved in the immunosuppressive function of Tregs. In this study, we investigated the effect of moxibustion on CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in dextran sulfate sodium (DSS) induced UC mice. The A2a receptor (A2aR), one of the targets of adenosine, was also detected. The results showed that moxibustion could increase the expression of CD39, CD73, and A2aR in colonic tissue and improve the proportion of CD39[Formula: see text] Tregs and CD73[Formula: see text] Tregs in peripheral blood, inguinal draining lymph nodes and spleen in the UC model. Additionally, A2aR agonists enhanced the cell viability of colonic epithelial cells and inhibit the production of cytokines IL-6 and TNF-[Formula: see text] in vitro, which may further influence the pathway of ATP purine signal metabolism and alleviates the gut inflammation of UC mice. Taken together, this study provides supplemental evidence to reveal the immune related mechanism of moxibustion in the treatment of UC.

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