Effects of TNF‐α, IFN‐γ and IL-β on normal human bronchial epithelial cells

Kampf, Caroline; Relova, A.J.; Sandler, Stellan; Roomans, G. M.

doi:10.1034/j.1399-3003.1999.14a15.x

Cited by 61 publications

(36 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LOS has been shown to act as an epithelial cytotoxin in organ cultures of rat trachea (32). Further cytokine production by the epithelial cells could then lead to further epithelial cell damage (25,36). Finally, Joseph et al (33) suggested that LPS could act as a structural analog of ceramide and hence could stimulate host cells by mimicking the second messenger function of ceramide.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, epithelial cells may act as sensors and play a key role in the modulation of the immune response to microbial infections (22,35,39). Further, IL-1 and TNF-␣ have been shown to damage respiratory epithelial cells (25,36), and H. influenzae has been shown to preferentially adhere to damaged epithelial cells (60,75). Thus, cytokineinduced respiratory epithelial cell damage may provide a means for H. influenzae to adhere to and invade host cells.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of Proinflammatory Cytokines from Human Respiratory Epithelial Cells after Stimulation by NontypeableHaemophilus influenzae

et al. 2000

View full text Add to dashboard Cite

Nontypeable Haemophilus influenzae (NTHi) causes repeated respiratory infections in patients with chronic lung diseases. These infections are characterized by a brisk inflammatory response which results in the accumulation of polymorphonucleated cells in the lungs and is dependent on the expression and secretion of proinflammatory cytokines. We hypothesize that multiple NTHi molecules, including lipooligosaccharide (LOS), mediate cellular interactions with respiratory epithelial cells, leading to the production of proinflammatory cytokines. To address this hypothesis, we exposed 9HTEo؊ human tracheal epithelial cells to NTHi and compared the resulting profiles of cytokine gene expression and secretion using multiprobe RNase protection assays and enzyme-linked immunosorbent assays (ELISA), respectively. Dose-response experiments demonstrated a maximum stimulation of most cytokines tested, using a ratio of 100 NTHi bacterial cells to 1 9HTEo؊ tracheal epithelial cell. Compared with purified LOS, NTHi bacterial cells stimulated 3.6-and 4.5-fold increases in epithelial cell expression of interleukin-8 (IL-8) and IL-6 genes, respectively. Similar results were seen with epithelial cell macrophage chemotactic protein 1, IL-1␣, IL-1␤, and tumor necrosis factor alpha expression. Polymyxin B completely inhibited LOS stimulation but only partially reduced NTHi whole cell stimulation. Taken together, these results suggest that multiple bacterial molecules including LOS contribute to the NTHi stimulation of respiratory epithelial cell cytokine production. Moreover, no correlation was seen between NTHi adherence to epithelial cells mediated by hemagglutinating pili, Hia, HMW1, HMW2, and Hap and epithelial cytokine secretion. These data suggest that bacterial molecules beyond previously described NTHi cell surface adhesins and LOS play a role in the induction of proinflammatory cytokines from respiratory epithelial cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Induction of Proinflammatory Cytokines from Human Respiratory Epithelial Cells after Stimulation by NontypeableHaemophilus influenzae

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Some of the retrieved transplanted islets were prepared for and studied with transmission electron microscopy (TEM), as previously described (17). Briefly, the retrieved islets were fixed overnight in 2.5% (vol/vol) glutaraldehyde (Sigma-Aldrich) and 0.1 mol/l cacodylate buffer (Agar Scientific, Stansted, U.K.).…”

Section: Methodsmentioning

confidence: 99%

Evidence of Functional Impairment of Syngeneically Transplanted Mouse Pancreatic Islets Retrieved from the Liver

Mattsson

Jansson²,

Nordin³

et al. 2004

Diabetes

View full text Add to dashboard Cite

A drawback in pancreatic islet transplantation is the large number of islets needed to obtain insulin independence in patients with diabetes. This most likely reflects extensive posttransplantation islet cell death and functional impairment of the remaining endocrine cells. We aimed to develop an experimental method to retrieve transplanted islets from the mouse liver, which would enable comparisons of transplanted and endogenous islets and provide valuable information on functional changes induced by intraportal transplantation. Transplanted islets were obtained by retrograde perfusion of the liver with collagenase. The identity of retrieved tissue as transplanted islets was confirmed by intravital staining, immunohistochemistry, and electron microscopy. The retrieved islets, irrespective of whether they had resided in diabetic or nondiabetic recipients, had a markedly lower insulin content and glucose-stimulated insulin release when compared with isolated endogenous islets. The glucose oxidation rate was also markedly lower in the retrieved islets, suggesting mitochondrial dysfunction. These disturbances in insulin content, insulin release, and glucose oxidation rate were not reversed by a few days of culture after retrieval. The results implicate changes in islet function after intraportal transplantation. Such dysfunction may contribute to the high number of islets needed for successful transplantation in diabetic individuals. Diabetes 53:948 -954, 2004 R ecent modifications in islet allotransplantation protocols, such as immunosuppressive treatment regimens without steroids and cyclosporine, as well as repeated transplantations to increase the implanted endocrine mass, have substantially increased the number of patients who achieve insulin independence (1-3). However, that two to three transplantations are usually needed to reverse hyperglycemia in humans suggests that the liver does not provide optimal conditions for engraftment. Indeed, although Ͼ85% of the normal islet mass (4) was transplanted when applying the Edmonton protocol, the insulin response to glucose in these patients was only ϳ20%, whereas the insulin response to arginine (ATP independent) was ϳ45% of that seen in healthy individuals (3,5). This suggests that islet cell death occurs in the immediate posttransplantation period (6,7) but may also indicate a functional impairment in the surviving endocrine cells.Experimental investigations (8 -11) on the endocrine function of intraportally transplanted islets have previously been performed by perfusion of whole rat livers containing transplanted islets. Even though this is an elegant approach, it does not enable functional comparisons to be made between endogenous and transplanted islets. Because the volume of the surviving islet mass is unknown, the contribution of islet death versus dysfunction of remaining islets to a poor insulin response is impossible to evaluate. Thus, to approach this problem of functional evaluation of intraportally implanted islets, we applied methods for enzymatic bre...

show abstract

“…However, in BALF recovered from rats instilled with 250, 500, and 1,000 g of LPS, 27 Ϯ 4, 299 Ϯ 162, and 472 Ϯ 84 EU/ml were detected, respectively. Cytokines associated with LPS-induced inflammation and MCM (14,16,19) were measured by ELISA. IL-6 and TNF-␣ levels were essentially unchanged (100-500 pg/ml) at all doses compared with saline-instilled controls, but IL-1␤ levels increased significantly from 0.01 Ϯ 0.007 in saline controls to 0.45 Ϯ 0.1, 1.1 Ϯ 0.35, 2.6 Ϯ 0.9, 15.4 Ϯ 6.4, and 30.1 Ϯ 2.8 ng/ml at 50-, 100-, 250-, 500-, and 1,000-g LPS doses, respectively (P Ͻ 0.05 for all LPS doses).…”

Section: And Bcl-2 Expression At 2 3 and 4 Days Post-lps Instilmentioning

confidence: 99%

LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells

Foster

Gott²,

Schuyler³

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Our previous studies show that Bcl-2, a regulator of apoptosis, may be involved in the reduction of mucous cell metaplasia (MCM) during recovery from inflammatory responses. The present study was to determine whether neutrophilic inflammation mediates Bcl-2 expression in mucous cells. Rats were intratracheally instilled with 50–1,000 μg of LPS. The number of neutrophils recovered by bronchoalveolar lavage (BAL) increased with the dose of LPS, and the percentage of Bcl-2-expressing cells increased with the numbers of neutrophils in the BAL. Depletion of neutrophils did not reduce MCM, but the percentage of Bcl-2-positive cells increased 1.8-fold in neutrophil-depleted compared with controls. Injection of rats with bezafibrate, an inducer of cytochrome P-450, doubled the number of neutrophils in the BAL, decreased MCM twofold compared with vehicle-injected controls, and reduced Bcl-2 expression. Bcl-2 mRNA levels decreased in a tracheal epithelial cell line treated with bezafibrate. These data demonstrate that Bcl-2 expression is independent of the number of neutrophils in the BAL and that bezafibrate may directly reduce Bcl-2 expression in epithelial cells.

show abstract

Effects of TNF‐α, IFN‐γ and IL-β on normal human bronchial epithelial cells

Cited by 61 publications

References 33 publications

Induction of Proinflammatory Cytokines from Human Respiratory Epithelial Cells after Stimulation by NontypeableHaemophilus influenzae

Induction of Proinflammatory Cytokines from Human Respiratory Epithelial Cells after Stimulation by NontypeableHaemophilus influenzae

Evidence of Functional Impairment of Syngeneically Transplanted Mouse Pancreatic Islets Retrieved from the Liver

LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells

Contact Info

Product

Resources

About