Release of arachidonic acid metabolites by human monocytes or lymphocytes: Effect of treatment with interferon on stimulation by phorbol ester or calcium lonophore

Hoffman, Thomas; Lizzio, Elaine F.; Ting, Andrew Chung Jie; Marshall, Lisa A.; Bonvini, Ezio; Jennings, M. K.

doi:10.1016/0090-1229(87)90054-7

Cited by 20 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…20 It has also been shown that in vitro gliadin challenge induces migration of CD3+ T cells to the subepithelial compartment in coeliac disease patients on a gluten free diet. 21 Prior studies have either failed to detect [22][23][24][25][26] or have detected only small amounts of prostaglandin synthesis 27 28 in lymphocyte cultures. However, two recent studies have shown that the COX-2 mRNA and protein are inducible in vitro in T lymphocytes activated by several stimuli that mimic T cell receptor/CD3 T cell activation.…”

Section: Discussionmentioning

confidence: 99%

Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2

Kainulainen

2002

Gut

View full text Add to dashboard Cite

Background and aims: Coeliac disease is characterised by atrophy of the villi and hyperplasia of the crypts in the mucosa of the small intestine. It is caused by an environmental trigger, cereal gluten, which induces infiltration of the mucosa by inflammatory cells. We hypothesised that these inflammatory cells express cyclooxygenase 2 (COX-2), an enzyme that contributes to the synthesis of pro and anti-inflammatory prostaglandins and is known to be expressed at sites of inflammation in the stomach and colon. We have investigated expression of COX-2 in the coeliac disease affected small intestinal mucosa where it may be an indicator of either disease induction or mucosal restoration processes. Patients and methods: Small intestinal biopsy samples from 15 coeliac patients and 15 non-coeliac individuals were stained immunohistochemically for COX-2. Samples from 10 of the patients were also stained after these patients had been on a gluten free diet for 6-24 months. Various cell type marker antigens were used for immunohistochemical identification of the type of cell that expressed COX-2. To further verify colocalisation of the cell type marker and COX-2, double immunoperoxidase and immunofluorescence methods were employed. Immunoelectron microscopy was used to investigate the subcellular location of COX-2. Results: In all samples taken from coeliac patients, clusters of cells with strong immunoreactivity for COX-2 were found in those areas of the lamina propria where the epithelium seemed to blister or was totally detached from the basement membrane. These clusters were reduced in number or totally absent in samples taken after a gluten free diet. No such clusters were seen in any control samples. The density of COX-2 positive cells lining the differentiated epithelium decreased significantly from 13.5 (5.1) cells/10 5 µm 2 (mean (SD)) in the untreated patient samples to 6.5 (2.0) cells/10 5 µm 2 after a gluten free diet (p<0.001), and was 3.3 (1.9) cells/10 5 µm 2 in control samples (p<0.001 compared with untreated or diet treated coeliac samples). Staining for COX-2 was localised to CD3+ T cells and CD68+ macrophages in the mucosal lesions but not all of these cells were positive for COX-2. Immunoelectron microscopy revealed that the ultrastructure of the COX-2 positive cells resembled that of lymphocytes, and the immunoreaction was localised to the rough endoplasmic reticulum and the nuclear envelope. Conclusions: Our results show that in coeliac disease, blistering of small intestinal epithelial cells is associated with accumulation of COX-2 positive T cells, and the number of these cells decreases after a gluten free diet. These observations suggest that COX-2 mediated prostanoid synthesis contributes to healing of the coeliac mucosa and may be involved in maintenance of intestinal integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2

Kainulainen

2002

Gut

View full text Add to dashboard Cite

show abstract

“…9). There are a number of cytotoxic molecules from macrophages that have low molecular mass (< 1 kDa) such as hydrogen peroxide (Nathan and Root, 1977), nitric oxide (Liew and Cox, 1991), leukotrienes (Hoffman et al, 1987), lipoxins (Pettitt et al, 1989), and su- (Johnston et al, 1978;. However, our assay systems (which preclude cell contact and require stability in culture medium) would probably not detect such highly reactive intermediates.…”

Section: Microglial Neurotoxins and Inflammatory Cell Poisonsmentioning

confidence: 99%

Brain glia release factors with opposing actions upon neuronal survival

1993

View full text Add to dashboard Cite

Microglia and astroglia have been thought to govern the survival of neurons after damage to the CNS. To investigate these putative glia-neuron relationships, we examined microglia and astroglia secretion products for effects upon growth of cultured neurons. Activated microglia secrete small neurotoxic factors (< 500 Da), while astroglia constitutively release proteins (> 10 kDa) that promote neuronal growth. Proteins released from astroglia, moreover, attenuate microglial toxicity, suggesting that different glial populations have opposing actions upon neuronal survival. Further study shows that neurotoxins from microglia are heat-stable, protease-resistant molecules with biologic activities blocked by NMDA receptor antagonists. Microglial factors, although toxic for chick ciliary neurons and rat spinal cord neurons, did not reduce numbers of oligodendroglia, astroglia, or Schwann cells in culture. The microglial neurotoxins can be distinguished from cytokines, from free radical intermediates, from the excitatory amino acids glutamate or aspartate, and from the NMDA receptor-mediated toxin quinolinic acid. We propose that secretion products from reactive microglia, but not astroglia, endanger surviving neurons after CNS injury by release of a novel class of neuron-killing molecules.

show abstract

“…We made the presupposition that by using interferon‐β, the risk of induction of pro‐inflammatory chemical mediators in the intestinal mucosa—which then triggers colitis—would be avoidable. The contradictory results which arose from earlier tests with interferon‐α in patients with chronic bowel disease could possibly have been caused by the inexact, non‐homogenous selection of patients, their pre‐therapeutic condition and treatments, and the impossibility of calculating the individual activation processes which promote pro‐inflammatory chemical mediators 27 . 28…”

Section: Introductionmentioning

confidence: 99%

Induction and maintenance of clinical remission by interferon‐β in patients with steroid‐refractory active ulcerative colitis—an open long‐term pilot trial

Musch

Andus

Malek

2002

Aliment Pharmacol Ther

View full text Add to dashboard Cite

Background: The imbalance of pro‐ and anti‐inflammatory cytokines plays an important role in the pathogenesis of inflammatory bowel disease. Shifting this disturbed ratio by means of TNF‐antibodies or interferon has been shown to be helpful in treating Crohn's disease and multiple sclerosis, respectively. Aim: This pilot study investigated whether interferon‐β can induce clinical remission in corticoid‐refractory ulcerative colitis. Methods: Twenty‐five patients with steroid‐refractory active ulcerative colitis (Clinical activity index according to Rachmilewitz: 13.5 ± 5.2) were treated in an open pilot trial with 0.5 MIU human natural interferon‐β (hn‐IFN‐β) i.v. (n=18) or 1 MIU recombinant interferon‐β‐1a (r‐IFN‐β‐1‐a) s.c. (n=7) daily with the goal of induction of remission. Subsequent maintenance treatment was carried out for 52.0 ± 78.8 weeks (range 4–336 weeks) with the same dose, three times per week. Results: Twenty‐two of 25 patients (88%) went into remission during induction treatment (hn‐IFN‐β 16/18, r‐IFN‐β‐1a 6/7). Mean time to response was 3.0 ± 1.3 weeks. Mean length of remission was 13.0 ± 19.7 months. Only eight of 22 patients in remission relapsed during maintenance treatment. Five of these went into remission again after increasing the dose. Adverse events consisted of slight to moderate flu‐like symptoms and slight to moderate hair loss in five of 15 female patients. Conclusion: Although this open pilot study included only a small number of patients, the high response rate suggests that interferon‐β may be a safe and effective treatment for steroid‐refractory active ulcerative colitis.

show abstract

Release of arachidonic acid metabolites by human monocytes or lymphocytes: Effect of treatment with interferon on stimulation by phorbol ester or calcium lonophore

Cited by 20 publications

References 20 publications

Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2

Blisters in the small intestinal mucosa of coeliac patients contain T cells positive for cyclooxygenase 2

Brain glia release factors with opposing actions upon neuronal survival

Induction and maintenance of clinical remission by interferon‐β in patients with steroid‐refractory active ulcerative colitis—an open long‐term pilot trial

Contact Info

Product

Resources

About