![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192, Japan
2To whom correspondence should be addressed.
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
B was assessed
with an electrophoretic gel mobility shift assay. The addition of oleic
acid (LCFA) micelles, but not octanoic acid (MCFA) micelles, weakly but
significantly enhanced basal IL-8 secretion in the intestine-407 cells.
The addition of MCFA (5 mmol/L) induced a 40% increase in
IL-1ß–induced IL-8 secretion and a 35% increase in tumor necrosis
factor (TNF)-
–induced IL-8 secretion, respectively. The addition of
LCFA (5 mmol/L) induced a 140% increase in IL-1ß–induced IL-8
secretion and a 110% increase in TNF-–induced IL-8 secretion,
respectively. These responses were also observed at the mRNA levels.
The electrophoretic gel mobility shift assay indicated that both MCFA
and LCFA enhanced IL-1ß– and TNF-–induced nuclear factor-B
activation. We demonstrated the proinflammatory activities of MCFA and
especially LCFA. It is likely that medium-chain triglycerides may
be more suitable than long-chain triglycerides as an energy source
in enteral diets in the treatment of patients with Crohn’s
disease.
KEY WORDS: • NF-B • Crohn’s disease • inflammation
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
, Tysk et al. 1988
), but it has also
been suggested that environmental factors, including dietary
components, might play an important role (Tragonone et al. 1995
). Furthermore, nutritional support in the correction and
maintenance of nutritional status in patients with IBD is widely
accepted (Greerling et al. 1999
, O’Sullivan et al. 1998
).
Several studies have demonstrated the primary therapeutic effects of
enteral nutrition in patients with Crohn’s disease (CD)
(O’Morain et al. 1984
, O’Sullivan et al. 1998
, Saverymuss et al. 1985
). In these studies,
the remission rates among patients treated with enteral diets were
comparable to those of patients administered corticosteroid therapy
(Saverymuss et al. 1985
, Seidman et al. 1986
). However, the mode of action of enteral nutrition as the
primary treatment of active CD patients remains conjectural.
Theoretically, several mechanisms have been proposed: bowel rest,
elimination of dietary antigen uptake, alterations in intestinal
microbial flora, nutritional repletion and modification of intestinal
permeability (O’Sullivan et al. 1998
). Among these
factors, the quantity and type of fat in enteral diets may have
important therapeutic effects. In previous reports of enteral feeding
trials in CD patients, it has been demonstrated that high-fat
formulas resulted in poorer outcomes, whereas low-fat diets were
associated with more favorable results (Fernandez-Banares et al. 1994
). Furthermore, fatty acid chain length affects the
response to enteral diets. Middleton et al. (1995)
demonstrated that remission rates of active CD patients were negatively
correlated with amounts of long-chain triglycerides (LCT), whereas
Khoshoo et al. (1996)
reported that there were no
differences in therapeutic efficacy between low and high
medium-chain triglyceride (MCT) diets in active CD patients.
Recently, we observed that LCT feeding markedly enhanced mucosal damage
compared with MCT feeding in trinitrobenzene sulfonic acid–induced
experimental enteritis in rats (Tsujikawa et al. 1999
).
These findings suggest the possibility that fats, especially LCT, may
enhance local inflammatory responses in the intestine. However, how fat
absorption modulates inflammatory responses in the intestinal mucosa
has not been fully investigated.
The cytokine interleukin (IL)-8 is a potent chemoattractant for
neutrophils, T cells and basophils. IL-8 induces the accumulation and
activation of neutrophils and initiates and promotes acute inflammatory
responses. In the intestinal mucosa, epithelial cells have been
regarded as a site of IL-8 secretion (Eckmann et al. 1993
, McDermott et al. 1998
, van Deventer 1997
). It has also been reported that epithelial IL-8 secretion
is potently enhanced by the proinflammatory cytokines tumor necrosis
factor (TNF)- and IL-1ß, released by activated
monocytes/macrophages. To evaluate the effects of MCT and LCT on the
inflammatory response in the intestine, we tested the effects of
medium- and long-chain fatty acids (MCFA and LCFA) on IL-8
secretion in the human fetal intestinal epithelial cell line
intestine-407 (Henle and Deinhardt, 1957
). LCT and MCT
are considered to be absorbed as LCFA and MCFA, respectively. The
present study provided data that indicate LCFA and MCFA differentially
modulate IL-1ß– and TNF-–induced IL-8 secretion in intestinal
epithelial cells.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Recombinant human IL-1ß (specific activity 2 x 107
U/mg by mouse thymocyte proliferation assay) was kindly provided by
Otsuka Pharmaceutical (Tokushima, Japan). Recombinant human TNF-
(specific activity 2.5 x 106 U/mg by cytotoxic assay
against LM cells) was kindly provided by Dainippon Pharmaceutical
(Osaka, Japan). All other reagents used in this study were purchased
from Sigma Chemical Co. (St. Louis, MO).
Cells.
The intestine-407 cells were obtained from American Type Culture
Collection (Rockville, MD). The cells were established from the small
intestine of a human fetus (Henle and Deinhardt 1957
),
retain a normal karyotype (data from American Type Culture Collection)
and exhibit typical epithelial morphology and growth. The cells are
used as a model of normal intestinal epithelial cells in vitro. For
example, the expression of the TNF- receptor has been identified in
these cells (Kawanishi 2000
). The cells were cultured as
a monolayer and maintained in Dulbecco’s modified Eagle’s medium
(GIBCO, Grand Island, NY) containing 10% fetal bovine serum (GIBCO), 5
x 104 U/L penicillin and 50 mg/L streptomycin. The
cells were seeded at a density of 2.5 x 108 cells/L,
and the cell culture medium was changed every 3rd d. All experiments
were performed after cells reached confluence.
Preparation of micellar solutions.
Micellar solutions were prepared according to the method described by
Johnston and Borgstrom (1964)
. We used oleic acid (18:1)
as the LCFA and octanoic acid (8:0) as the MCFA. Oleic acid and
mono-olein were dissolved in benzene, dried under nitrogen and
dissolved in 40 mmol/L taurocholate. The solution was diluted with an
equal volume of 0.125 mol/L NaCl plus 0.017 mol/L phosphate buffer (pH
7.4). The final concentration contained 20 mmol/L sodium taurocholate,
19.2 mmol/L oleic acid and 9.6 mmol/L mono-olein. A solution of
19.2 mmol/L octanoic acid in phosphate buffer with 20 mmol/L
taurocholate was similarly prepared. A solution of 20 mmol/L
taurocholate in phosphate buffer was also prepared as a control.
Quantification of human IL-8.
The amounts of antigenic IL-8 in the samples were determined with enzyme-linked immunosorbent assay kits (Cytoscreen Human IL-8, catalogue no. KHC0082; Bio Source, Camarillo, CA). Intestine-407 cells were incubated for 12 h, and then IL-8 levels in supernatants were determined with enzyme-linked immunosorbent assay. As a control, cells were incubated in the medium containing taurocholate alone (same concentration in both MCFA and LCFA media).
Northern blot analysis for IL-8 mRNA expression.
Intestine-407 cells were stimulated for 3 h, and then IL-8 mRNA
expression was analyzed by Northern blotting. Samples of total RNA (20
µg), isolated according to the method described by Chomczynski et al. (1987)
, were denatured in a loading buffer for 15 min at
65°C. The RNA was then electrophoresed through a 1.0%
agarose-formaldehyde gel and transferred to a nylon membrane (Gene
Screen Plus; New England Nuclear Research Products, Boston, MA) in a
10x SSPE solution. After the transfer, the membrane was washed and
baked at 80°C for 2 h. The prehybridization was performed for
4 h at 42°C in a solution containing 50% formamide, 5x SSPE,
1x Denhardt’s solution, 0.2% sodium dodecyl sulfate and 100 mg/L
denatured salmon sperm DNA. The hybridization was performed with
32P-labeled human IL-8 probe, generated with a random
primed DNA labeling kit (Amersham, Arlington Heights, IL) and evaluated
with autoradiography.
Nuclear extracts and electrophoretic gel mobility shift assays.
Nuclear extracts were prepared from intestine-407 cells after a 2-h
stimulation according to the method of Dignam and Roeder (1983)
. Consensus oligonucleotides of NF-B (5'-AGT TGA
GGG GAC TTT CCC AGC C) were used (Lenardo and Baltimore 1989
). The consensus sequence for the binding of each
transcription factor is underlined. Oligonucleotides were 5'
end-labeled with T4 polynucleotide kinase (Promega, Madison, WI)
and [
-32P]ATP (Amersham). Binding reactions were
performed by preincubating 7.5 µg of nuclear protein in 20 mol/L
HEPES, pH 7.9, 60 mol/L KCl, 1 mol/L MgCl2, 0.1 mol/L EDTA,
10% glycerol, 0.5 mol/L dithiothreitol and 2 µg of poly(dI/dC) on
ice for 10 min, followed by the addition of 32P-labeled
oligonucleotide and a second incubation at room temperature for 20 min.
Samples were loaded directly onto nondenaturing 4% polyacrylamide gels
prepared in Tris-glycine-EDTA buffer (pH 8.5). The gels were dried and
exposed to Kodak XRP film with an intensifying screen. Supershift
experiments were performed as described except that 1 µL of antibody
to transcription factor was added to the binding mixture in the absence
of the labeled probe. Antiserum specifically recognizing
transcriptional factor was purchased from Santa Cruz Biotechnology
(Santa Cruz, CA). Experiments with unlabeled oligonucleotides used a
100-fold molar excess relative to the radiolabeled oligonucleotide.
Measurement of radioactivity.
The radioactivity of each band of Northern blots and electrophoretic gel mobility shift assay was determined with the Instant Imager Electronic Autoradiography system (model 2024/417257;Packard,Meriden,CT). For comparison, absolute radioactivity was converted to a value relative to the radioactivity of the medium alone.
Statistical analysis.
The data are expressed as means ± SD. The variance was analyzed by the Bartlett test (Statview for Macintosh Version 4.5; Abacus Concepts, Berkeley, CA). Subsequently, statistical significance of differences was determined by the Fisher’s PLSD (Protected Least Significance Difference) test (Statview for Macintosh Version 4.5). Differences resulting in P-values of <0.05 were considered statistically significant.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
–induced IL-8 secretion (Fig. 1
). These effects were observed at concentrations as low as 1.0 mmol/L
(P < 0.05). LCFA dose-dependently enhanced
IL-1ß– and TNF-–induced IL-8 secretion (Fig. 2
). These effects were also observed at concentrations as low as 1.0
mmol/L (P < 0.05). When the effects of MCFA (5 mmol/L)
and LCFA (5 mmol/L) were compared, LCFA enhanced IL-1ß (10
µg/L)–induced IL-8 secretion more strongly than MCFA (IL-1ß plus
MCFA 94.6 ± 3.8, IL-1ß plus LCFA 185.6
± 13.3, P < 0.01). Similarly, the effects of
LCFA (5 mmol/L) on TNF- (10 µg/L)–induced IL-8 secretion were
significantly stronger than those of MCFA (5 mmol/L) (TNF- plus MCFA
85.6 ± 3.8, TNF- plus LCFA 138.8 ± 10.2, P
< 0.01).
|
|
–induced IL-8 mRNA expression (Fig. 3
). The effects of LCFA on mRNA were stronger than those of MCFA
(P < 0.05), compatible with findings at the protein
level.
|
for 2 h increased
NF-B–DNA binding activity (Fig. 4
, lanes 2 and 5). The specificity of this reaction was confirmed by the
addition of cold oligo-DNA, in which the reactive band disappeared
(lane 8). The addition of antibodies to a 50,000 molecular weight
subunit (p50) of NF-B and the 65,000 molecular weight subunit (p65)
induced supershifts of the binding complexes (lanes 9 and 10),
indicating that this binding complex was a heterodimer that consists of
the p50 and p65 subunits. The addition of MCFA enhanced the IL-1ß–
and TNF-–induced activation of NF-B binding activity (lanes 3
and 6). Similarly, LCFA enhanced the IL-1ß– and TNF-–induced
activation of NF-B binding activity (lanes 4 and 7). The effects of
LCFA were stronger than those of MCFA (P < 0.05),
suggesting that the effects of both MCFA and LCFA were mediated by
signal transduction through the NF-B activation pathway.
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
,
Miller et al. 1992
). Although many different cell types,
including monocytes/macrophages, fibroblasts and endothelial cells, can
secrete IL-8 (Baggiolimi et al. 1994
), epithelial cells
have been established as one of the main biosynthetic sites in the
intestine (Eckmann et al. 1993
, McDermott et al. 1998
, van Deventer 1997
). IL-8 is a key cytokine
for the recruitment and activation of neutrophils, which are abundant
in the intestinal lesions of IBD (McDermott et al. 1998
,
van Deventer 1997
). In the present study, we tested the
effects of MCFA and LCFA on IL-8 secretion in human fetal intestinal
epithelial cells. Our results indicated that MCFA and LCFA
significantly enhanced IL-1ß– and TNF-–induced IL-8 secretion in
these cells. LCFA alone also weakly but significantly stimulated basal
IL-8 secretion. These findings suggest that the absorption of MCFA and
LCFA may play an important role in the progression and maintenance of
local inflammation in the intestine. It is likely that the enhancement
of IL-8 secretion in intestinal epithelial cells may result in the
continuous recruitment of neutrophils and the prolongation of local
inflammation in the intestine, reducing the remission rate or response
to therapy in IBD patients. LCFA enhanced IL-1ß– and
TNF-–induced IL-8 secretion more than did MCFA. These results are
consistent with the clinical reports that high LCT feeding, but not MCT
feeding, reduces the remission rate of active CD patients
(Khoshoo et al. 1996
, Middleton et al. 1995
). Thus, the proinflammatory nature of MCFA and LCFA was
demonstrated, and there were differences between their proinflammatory
effects.
The transcription factor NF-B is important in the transcriptional
activation of genes encoding the proteins that participate in
inflammatory and immune responses (Lenardo and Baltimore 1989
). NF-B activation is regulated by its cytoplasmic
association with IB molecules (inhibitors of nuclear factor for
immunoglobulin chain in B cells), which mask the nuclear
localization signal of NF-B. In most cells, IB is the
predominant inhibitory molecule, and the activation and translocation
of NF-B into the nucleus are contingent on its release from
IB. Numerous stimuli, including IL-1ß and TNF-, rapidly
induce the proteolytic degradation of IB and the consequent
activation of NF-B. The promoter region of the human IL-8 gene has
been cloned, sequenced and shown to contain putative consensus binding
motifs for NF-B (Kunsh et al. 1994
, Yasumoto et al. 1992
). In vivo mucosal NF-B activation has been
reported to correlate with the disease activity of IBD patients
(Schreiber et al. 1998
). Our results indicated that the
enhancing effects of MCFA and LCFA on IL-8 secretion were correlated
with the increase in NF-B activation in intestinal epithelial cells.
Furthermore, IL-1ß– and TNF-–induced NF-B activation was more
potently enhanced by the addition of LCFA than of MCFA. These findings
suggest that various inflammatory responses, which are mediated by
NF-B activation, may be enhanced by MCFA and especially LCFA in the
intestinal mucosa. In the therapeutic strategies for CD patients, these
results suggest that MCT rather than LCT should be used as an energy
source in enteral diets because of their lower proinflammatory
activity.
The replacement of dietary LCT by MCT reduces both steatorrhea and
diarrhea as well as fecal electrolyte excretion in patients with a
reduced small intestinal mucosal area due to resection or disease
(Greenberger and Skillmann 1969
, Hot 1968
, Jeppensen and Mortensen 1998
). These
effects are considered to be associated with the rapid absorption of
MCT, which is not dependent on micelle formation, intraluminal
hydrolysis and mucosal reesterification (Greenberger and Skillmann 1969
, Hot 1968
). The human colon is
not usually considered to be a site of fat absorption, but several
experiments have indicated that because of their water solubility, MCFA
are effectively absorbed in the colon (Jeppensen and Mortensen 1998
). These nutritional characteristics of MCT or MCFA also
make them suitable energy sources for CD patients, because multiple
ulceration and mucosal inflammation in the small intestine markedly
decrease absorption. Combined results suggest that MCT are potentially
beneficial in the nutritional treatment of CD patients for two reasons:
1) more rapid absorption in the small and large bowel
and 2) less proinflammatory activity.
In conclusion, we demonstrated differences between MCFA and LCFA in
their proinflammatory activities. Both MCFA and LCFA enhanced IL-1ß–
and TNF-–induced inflammatory responses in intestinal epithelial
cells, but the effects of LCFA were stronger than those of MCFA. To our
knowledge, this is the first report demonstrating differences in
proinflammatory activity between MCFA and LCFA. Our findings suggest
that MCT may be more suitable than LCT as an enteral energy source in
the treatment of CD patients.
|
FOOTNOTES |
|---|
3 Abbreviations used: CD, Crohn’s disease; IBD, inflammatory bowel disease; IL, interleukin; LCFA, long-chain fatty acid; LCT, long-chain triglyceride; MCFA, medium-chain fatty acid; MCT, medium-chain triglyceride; NF-B, nuclear factor-B; TNF, tumor necrosis factor.
Manuscript received May 30, 2000. Initial review completed June 26, 2000. Revision accepted August 2, 2000.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1. Baggiolimi M., Dewald B., Moser B. Interleukin-8 and related chemotactic cytokines: CXC and CC chemokines. Adv. Immunol. 1994;55:97-179[Medline]
2. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 1987;162:156-159[Medline]
3.
Dignam J. P., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucl. Acids Res. 1983;11:1475-1489
4. Eckmann L., Jung H. C., Schurer-Maly C., Panja A., Morzycka Wroblewska E., Kagnoff M. F. Differential cytokine expression by human intestinal epithelial cell line: Regulated expression of interleukin 8. Gastroenterology 1993;105:1689-1697[Medline]
5. Fernandez-Banares F., Cabre E., Gonzalez-Huix F., Gasull M. A. Enteral nutrition as primary therapy in Crohn’s disease. Gut 1994;1(suppl.):55-59
6. Geerling B. J., Stockbrugger R. W., Brummer R.J.M. Nutrition and inflammatory bowel disease: An update. Scand. J. Gastroenterol. 1999;34(suppl.):95-105
7. Greenberger N. J., Skillmann T. G. Medium chain triglycerides: Physiological considerations and clinical implications. N. Engl. J. Med. 1969;280:1045-1058
8. Henle G., Deinhardt F. The establishment of strains of human cells in tissue culture. J. Immunol. 1957;79:54-59
9. Hot P. R. Medium chain triglycerides: Their absorption, metabolism and clinical applications. Glass B.G.J. eds. Progress in Gastroenterology 1968:277-298 Grune & Stratton New York, NY.
10.
Jeppesen P. B., Mortensen P. B. The influence of a preserved colon on the absorption of medium chain fat in patients with small bowel resection. Gut 1998;43:478-483
11. Johnston J. M., Borgstrom B. The intestinal absorption and metabolism of micellar solutions of lipids. Biochim. Biophys. Acta 1964;84:412-423
12.
Kawanishi M. The Epstein-Barr virus latent membrane protein 1 (LMP1) enhances TNF--induced apoptosis of intestine 407 epithelial cells: The role of LMP1 C-terminal activation regions 1 and 2. Virology 2000;270:258-266[Medline]
13.
Khoshoo V., Reifen R., Neuman M. G., Griffiths A., Pencharz P. B. Effect of low- and high-fat, peptide-based diets on body composition and disease activity in adolescents with active Crohn’s disease. J. Parenteral. Enteral Nutr. 1996;20:401-405
14.
Kitamura K., Andoh A., Inoue T., Amakata Y., Hodohara K., Fujiyama Y., Bamba T. Sodium butyrate blocks interferon-gamma (IFN-)-induced biosynthesis of MHC class III gene products (complement C4 and factor B) in human fetal intestinal epithelial cells. Clin. Exp. Immunol. 1999;118:16-22[Medline]
15. Kunsh C., Lang R. K., Rosen C. A., Shannom F. Synergistic transcriptional activation of the IL-8 gene by NF-kappa B p65 (RelA) and NF-IL6. J. Immunol. 1994;153:153-164[Abstract]
16.
Lenardo M. J., Baltimore D. NF-B: Pleiotropic mediator of inducible and tissue-specific gene control. Cell 1989;58:227-229[Medline]
17. McDermott R. P., Sanderson I. R., Reinecker H. C. The central role of chemokines (chemotactic cytokine) in the immunopathogenesis of ulcerative colitis and Crohn’s disease. Inflamm. Bowel Dis. 1998;4:54-67[Medline]
18. Middleton S. J., Rucker J. T., Kirby G. A., Riordan A. M., Hunter J. O. Long-chain triglycerides reduce the efficacy of enteral feeds in patients with active Crohn’s disease. Clin. Nutr. 1995;14:229-236
19. Miller M. D., Krangel M. S. Biology and biochemistry of the chemokines: A family of chemotactic and inflammatory cytokines. Crit. Rev. Immunol. 1992;12:17-46[Medline]
20. Nakajima A., Matsuhashi N., Kodama T., Nazaki Y., Takazoe M., Kimura A. HLA linked susceptibility and resistance gene in Crohn’s disease. Gastroenterology 1995;109:1462-1467[Medline]
21. O’Morain C., Segal A. W., Levi A. J. Elemental diet as primary treatment of acute Crohn’s disease. Br. Med. J. 1984;288:1859-1862
22. O’Sullivan M. A., O’Morain C. A. Nutritional therapy in Crohn’s disease. Inflamm. Bowel Dis. 1998;4:45-53[Medline]
23.
Saverymuss S., Hodgson H.J.F., Chadwick V. S. Controlled trial comparing prednisolone with an enteral diet plus non-absorbable antibiotics in active Crohn’s disease. Gut 1985;26:994-998
24.
Schreiber S., Nikolaus S., Hampe J. Activation of nuclear factor kappa B in inflammatory bowel disease. Gut 1998;42:477-484
25. Seidman E. G., Bouthillier L., Weber A. M., Roy C. C., Morin C. L. Elemental diet versus prednisone as primary treatment of Crohn’s disease. Gastroenterology 1986;90:A1625(abs.)
26. Tragonone A., Valpiani D., Miglio F., Elmi G., Bazzocchi G., Pipitone E., Lanfranchi G. A. Dietary habits as risk factors for inflammatory bowel disease. Eur. J. Gastroenterol. Hepatol. 1995;7:47-51[Medline]
27. Tsujikawa T., Ohta N., Nakamura T., Satoh J., Uda K., Ihara T., Okamoto T., Araki Y., Andoh A., Sasaki M., Fujiyama Y., Bamba T. Medium-chain triglycerides modulate ileitis induced by trinitrobenzene sulfonic acid. J. Gastoenterol. Hepatol. 1999;14:1166-1172[Medline]
28.
Tysk C., Lindberg C., Jarnerot G., Floderus-Myrhed B. Ulcerative colitis and Crohn’s disease in an unselected population of monozygotic and dizygotic twins: A study of heritability and the influence of smoking. Gut 1988;29:990-996
29. van Deventer S. J. Chemokine production by intestinal epithelial cells: A therapeutic target in inflammatory bowel disease?. Aliment. Pharmacol. Ther. 1997;11(suppl. 3):116-120
30.
Yasumoto K., Okamoto S., Mukaida N., Murakami S., Mai M., Matsushima K. Tumor necrosis factor and interferon synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-B-like binding sites of the interleukin 8 gene. J. Biol. Chem. 1992;267:22506-22511
This article has been cited by other articles:
|
|
 |
|
  A. Buenestado, J. Cortijo, M.-J. Sanz, Y. Naim-Abu-Nabah, M. Martinez-Losa, M. Mata, A. C. Issekutz, E. Marti-Bonmati, and E. J. Morcillo Olive Oil-Based Lipid Emulsion's Neutral Effects on Neutrophil Functions and Leukocyte-Endothelial Cell Interactions JPEN J Parenter Enteral Nutr, July 1, 2006; 30(4): 286 - 296. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
