 1, Interleukin-8 and
Interleukin-1, in Non-Small-Cell Lung Tumors
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
ABSTRACT |
|---|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
A role in tumor progression has been proposed for transforming growth fractor-
1 (TGF1) and interleukin (IL)-8 as well as for IL-1, which itself induces the production of TGF1 and IL-8 in many cell
types. TGF1 and IL-8 production and their regulation by IL-1 in five non-small-cell (NSC) lung tumor
cell lines were evaluated. Moreover, their levels were evaluated in 29 NSC lung tumors. All cell lines
constitutively produced TGF1, and three produced IL-8. After IL-1 treatment, TGF1 production
was upregulated in two cell lines, whereas IL-8 production was markedly upregulated in two, induced
in one, and unmodified in two. In tumors, the levels of TGF1, IL-8, and IL-1 were higher than in
normal counterparts (p < 0.001), and a positive correlation between IL-8 and IL-1 levels (p < 0.001)
was found. TGF1, IL-8, and IL-1 mRNA expression was examined in 12 tumors. TGF1 mRNA was
detected in all cases, IL-8 mRNA in 7, and IL-1 MRNA was undetectable. TGF1, IL-8, and IL-1 immunoreactivity was then studied by immunohistochemistry. TGF1 and IL-8 immunoreactivity was
observed in neoplastic cells; IL-1 immunoreactivity was observed in mononuclear cells. In conclusion, in tumors IL-1 levels positively correlated with those of IL-8, and IL-1 as well as TGF1 and IL-8
levels were significantly higher than in normal tissues.
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Involvement of cytokines in lung cancer pathogenesis and
progression has been proposed (1). Cytokines can be produced in the microenvironment of a tumor and influence its
cell growth via both autocrine and paracrine mechanisms. Several lines of evidence suggests that transforming growth factor-1 (TGF1), interleukin-8 (IL-8), and IL-1 play a role in
tumor progression. TGF1 inhibits the growth of normal epithelial cells; resistance to this inhibitory activity or proliferation in response to TGF1 by neoplastic cells are mechanisms
of tumor progression (4, 5). TGF1 has angiogenic properties
(6, 7), as well as the ability to increase the invasive and metastatic potential of neoplastic cells (8). Some of its immunoregulatory properties such as inhibition of T-cell proliferation
and deactivation of natural killer (NK) cells and macrophages
(11, 12) may enable tumor cells to evade immune surveillance.
Lung tumor cell lines can secrete TGF1, and these cells frequently do not respond to TGF1 or they can even be stimulated to proliferate (13). Recently, it has been reported in
an immunohistochemical study on lung adenocarcinomas that
TGF1-positive staining of neoplastic cells could be an unfavorable prognostic factor (16). Nevertheless, to our knowledge, no quantitative data about TGF1 levels in lung tumors
have been published.
IL-8 can be produced by non-small-cell (NSC) lung tumor cell lines (17, 18). It has been found to be present at high levels in lung squamous cell carcinomas and adenocarcinomas (19). IL-8 is a potent angiogenic factor (3), and treatment with IL-8-neutralizing antibodies has been found to reduce tumor size and vascular density in a model of human NSC lung cancer tumorigenesis in SCID mice (20).
IL-1 promotes angiogenesis and favors a prometastatic environment (21). Moreover, IL-1 induces production of TGF1
and IL-8 in many cell types (22), and upregulates IL-8 production in some lung tumor cell lines (17, 18). The effect of IL-1
on TGF1 production in lung tumor cell lines has not been investigated, and an increase of IL-1 levels in NSC lung tumors
has not been demonstrated.
The present study describes the production and mRNA expression of TGF1 and IL-8 and their regulation by IL-1 in
five NSC lung tumor cell lines. Moreover, TGF1, IL-8, and
IL-1 are studied in 29 NSC lung tumors.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Cell Lines and Culture Conditions
Lung cell lines obtained from the American Type Culture Collection
(Rockville, MD) (SK-LU1 poorly differentiated adenocarcinoma, SW900 squamous carcinoma, ChaGo-K-1 bronchogenic carcinoma,
H441 papillary adenocarcinoma, H661 poorly differentiated carcinoma) were maintained in RPMI 1640 medium supplemented with
10% fetal calf serum (FCS), 1% penicillin-streptomycin, and 2 mM
glutamine (Gibco, Paisley, UK). Cells were plated at 2 × 104/cm2 in
3.8 cm2 per well of 12-well plates (Falcon; Becton Dickinson, Oxnard, CA) in 10% FCS medium and grown to 5 × 104/cm2. They were then
cultured in fresh serum-free medium with or without human IL-1
(100 U/ml) (Peprotech, London, UK). At the indicated times the culture supernatants were collected, centrifuged to remove cellular debris, and frozen at 
20° C until assayed. Cells were harvested by
trypsinization, and hemocytometer counts of triplicate cultures were
performed. The cell viability at all time points was greater than 90%
as assessed by trypan blue staining.
Tissues
Lung tumor tissues (n = 29) were obtained from patients undergoing
thoracotomy for primary lung tumor; control normal lung tissues (n = 18) were obtained from areas distal to the tumor (Table 1). This study
was approved by the Institutional Ethics Committee. Tissue samples
were homogenized, processed for protein isolation, and frozen at
80° C until assayed. Protein concentration of tissue homogenates
was determined by Biorad Protein assay (BioRad, Richmond, CA).
Representative samples of tumor and normal tissues were frozen immediately and maintained at 80° C, or fixed and paraffin-embedded
until use.
|
Enzyme-linked Immunosorbent Assay (ELISA)
The levels of immunoreactive TGF1, IL-8, IL-1, and IL-1
were
measured with specific kits: Biotrak IL-8 (sensitivity, 5 pg/ml), IL-1
(sensitivity, 1 pg/ml), and IL-1 (sensitivity, 0.2 pg/ml) (Amersham,
Little Chalfont, UK) and Predicta TGF1 (sensitivity, 0.05 ng/ml)
(Genzyme, Cambridge, MA).
Northern Analysis
Total RNA extracted using the guanidine-isothiocyanate/CsCl gradient method was size-fractioned on denaturing 1% agarose gel with 2.2 mol formaldehyde and then transferred to nylon membrane filters by
capillary blotting. Blots were exposed to 32P-labeled specific DNA
probes. After hybridization, filters were washed and autoradiographed
at 80° C using Kodak XAR film (Eastman Kodak, Rochester, NY).
The following human cDNA fragments were prepared: IL-1 (Ndel,
Bam HI, 530 bp) from Dr. P. Lomedico (Hoffmann La Roche, Nutley,
NJ; IL-1 (Pstl, EcoRI, 1600 bp) from Dr. M. Palladino (Genentech
Inc., San Francisco, CA); IL-8 (EcoRI, 480 bp) from Dr. A. Mantovani (Mario Negri Institute, Milano, Italy); TGF1 (EcoRI, 1050 bp)
from Dr. R. Derynck (Genentech Inc.); 18SrRNA (Hind III, 3,000 bp) from Dr. C. Milcarek (University of Pittsburgh, Pittsburgh, PA)
and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (BamHI,
1,464 bp) from Dr. P. Arcari (University of Napoli, Napoli, Italy). The
cDNA fragments were labeled with [32P]dCTP (Amersham) using a
kit for random hexanucleotide priming (Boehringer-Mannheim Biochemicals, Indianapolis, IN).
Immunohistology
Formalin-fixed, paraffin-embedded sections and acetone-fixed cryostat sections wee stained by the streptavidine biotine HRP method
(Dakopatts, Glostrup, Denmark). The primary antibodies were antihuman TGF1 mouse monoclonal antibody (clone TB21; Serotec, Oxford, UK) and antihuman IL-8 and IL-1 rabbit polyclonal antibodies, from Dr. A. Mantovani (Milano, Italy). As negative control,
the first antibody was omitted or replaced with an irrelevant matched antibody.
Statistical Analysis
The results of the experiments performed with the cell lines are expressed as the mean ± SD. Student's t test for paired data was performed for statistical analysis. Comparisons between levels of cytokines in normal and tumor tissues were analyzed by nonparametric Mann-Whitney and Spearman's correlation tests. Statistics for nonpaired data were adopted because of a difference in number between the tumor and the normal tissue samples.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Production of TGF1 and IL-8 and Their Regulation by
IL-1 in Lung Tumor Cell Lines
Cell lines varied in their ability to produce TGF1. At 24 h,
TGF1 was detected in the supernatants of all cell lines and increased in a time-dependent manner (Figure 1a). The levels
of IL-8 in the supernatants of SW900 and H441 cells were very
low at 24 h, and then increased at 48 and 72 h in a time-dependent manner. SK-LU1 cells showed a low level of IL-8 production only at 72 h. H661 and ChaGo-K-1 cells did not produce
IL-8 at any time point (Figure 1b). No increase in the cell
number or decrease in cell viability were observed (data not
shown).
|
We next examined the effect of IL-1 on TGF1 and IL-8
production. Supernatants of cells cultured with or without IL-1 (100 U/ml) were collected at 24 h and assayed for TGF1
and IL-8. In the presence of IL-1, TGF1 levels were unmodified in SK-LU1, H441, and H661 supernatants, and significantly increased (p < 0.01) in SW900 and ChaGo-K-1 supernatants (Figure 2a). IL-1 induced IL-8 in ChaGo-K-1
cells and significantly increased (p < 0.001) IL-8 in the SK-LU1 and the SW900, but not in the H441 supernatants; H661
cells did not produce detectable levels of IL-8 either in the
presence or in the absence of IL-1 (Figure 2b). No constitutive production of IL-1 or was observed, and cell proliferation was not affected by IL-1, as assessed by cell counting
and tritiated thymidine incorporation (data not shown).
|
TGF1 and IL-8 mRNA expression was studied in parallel
cultures by Northern blot analysis (Figure 3). All cell lines expressed constitutive levels of TGF1 mRNA. IL-1 treatment
increased TGF1 expression in SW900, ChaGo-K-1, and SK-LU1 cells. Cell lines did not express detectable levels of IL-8
mRNA. IL-1 treatment markedly increased its expression in
SK-LU1, SW900, and ChaGo-K-1 cells.
|
TGF1, IL-8, and IL-1 in NSC Lung Tumors
Samples from normal and NSC lung tumor tissues were assayed for TGF1, IL-8, and IL-1 (Table 1). TGF1 and IL-8
were detected in normal (mean values: TGF1 = 836 pg/mg;
IL-8 = 146 pg/mg; n = 18) and in tumor tissues (mean values:
TGF1 = 1,471 pg/mg; IL-8 = 2,164 pg/mg; n = 29). Their levels were significantly higher in tumor tissues than in normal
tissues (Mann-Whitney U-test: TGF1, z = 4.67, p < 0.001;
IL-8, z = 5.05, p < 0.001). IL-1 was detected in only three of
18 normal tissue samples (16.6%), whereas it was present in 24 of 29 tumor tissue samples (82.7%). IL-1 was undetectable
both in normal and in tumor tissues (data not shown). There
were no differences in TGF1, IL-8, and IL-1 levels among
the histologic tumor subtypes (Table 1). A scattergram of
TGF1, IL-8, and IL-1 values is shown in Figure 4.
|
We then studied the distribution of TGF1 and IL-8 levels
relative to IL-1 levels in tumors (Figure 5a, b). IL-8 and IL-1 levels were positively correlated (Spearman's correlation
test, r = 0.617, p < 0.001), whereas no correlation was obtained on comparing TGF1 levels with IL-1 levels (r = 0.322, p < 0.089).
|
Lung tumor tissue samples were analyzed for TGF1, IL-8,
and IL-1 mRNA expression by Northern blot analysis (n = 12). TGF1 mRNA expression was variable, but it was always
evident. IL-8 mRNA expression was evident in five tumors,
barely detectable in two, and undetectable in five (Figure 6).
It was noted that those tumors that expressed IL-8 mRNA
produced high levels of IL-8 protein. The five tumors with evident IL-8 mRNA expression (lanes a, d, f, l, and m in Figure 6)
had IL-8 protein levels ranging between 2,675 and 8,500 pg/mg
(Tissue No's 27, 2, 13, 5, and 28; Figure 6 versus Table 1). The
tumors with barely detectable or undetectable IL-8 mRNA
expression (lanes b, h, c, r, g, i, and n in Figure 6) had IL-8 protein levels ranging between 165 and 1,125 pg/mg (Tissue No's
20, 17, 3, 1, 4, 15, and 16; Figure 6 versus Table 1). All tumors
had detectable protein levels; however, only five were positive
for IL-8 mRNA expression. A possible explanation could be
that in airway epithelial cells IL-8 mRNA has a low basal level
(17, 25) as well as a short half-life (25, 26), the latter probably
because of sequences in its 3' untranslated region that confer
susceptibility to degradation (27). It is likely that the number
of IL-8 mRNA copies in tumors with undetectable IL-8
mRNA expression was too low to be detected, considering the
sensitivity of Northern analysis (5 pg of a specific mRNA per
10 µg of total RNA) (28), whereas the ELISA method is 10 times more sensitive. Both TGF1 mRNA and protein were
present in all cases tested (Figure 6 versus Table 1). IL-1 and
IL-1 mRNA were undetectable. In normal lung tissues, TGF1
mRNA was expressed at varying levels, whereas IL-8 and IL-1
and mRNA were undetectable (data not shown).
|
By immunohistochemical analysis, TGF1 and IL-8 immunoreactivity was observed in neoplastic cells, whereas IL-1
immunoreactivity was observed in mononuclear cells; in normal lung tissue, epithelial cells were negative for TGF1, IL-8,
and IL-1 (Figure 7).
|
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
In this study the levels of TGF1, IL-8, and IL-1 were evaluated in parallel in NSC lung tumor specimens. Moreover, we
studied the influence of IL-1 on TGF1 and IL-8 production
in five NSC lung tumor cell lines.
All cell lines constitutively produced TGF1 and displayed
TGF1 mRNA expression. IL-1 induced an increase in
TGF1 protein levels and mRNA expression in SW900 and in
ChaGo-K-1 cells. An IL-1-induced increase of TGF1 protein
accompanied by increased mRNA expression has been previously observed also in endothelial and smooth muscle cells in
vitro (22, 23). In SW900 and in ChaGo-K-1 cells mean percentage increases in TGF1 mRNA expression of 31 ± 4 and
13 ± 3% (means of three experiments ± SE, as assessed by
image analysis, data not shown) were accompanied by 25 and 30% increases of the protein levels, respectively. Although in SK-LU1 cells a mean percentage mRNA expression increase
of 9 ± 2% was detectable, it was not accompanied by an increased protein level. This could be due to the regulation of
the post-transcriptional, assembly, and secretion mechanisms
controlling TGF1 production, which can cause discrepancies
between TGF1 mRNA and protein levels, both in normal
and in neoplastic cells (29, 30).
In tumors, as in the cell lines, TGF1 mRNA expression
was always present. No quantitative data about TGF1 levels
in lung tumors were available, although neoplastic cell TGF1
immunoreactivity has been correlated with a poor prognosis
in lung adenocarcinomas (16). We found that the mean TGF1
level was 1.7 times higher in tumors than in normal tissues. It
is noteworthy to mention that an increase in TGF1 levels has
been correlated with tumor progression also in breast and
pancreas tumors (31, 32).
The mean IL-1 level was 17.6 times higher than in normal
tissues. To our knowledge, this is the first demonstration of an increase of IL-1 in NSC lung tumors.
Although IL-1 upregulated TGF1 production in two cell
lines in vitro, no correlation between TGF1 and IL-1 levels
was found in tumors. The influence of IL-1 on TGF1 levels
could be absent in tumors, or other factors besides IL-1 may
contribute in regulating TGF1 production in vivo.
In agreement with previous data (17, 18), we observed that
IL-1 was a potent stimulus for IL-8 production and mRNA expression in lung tumor cell lines. The mean IL-8 level was 14.8 times higher in tumors than in normal tissues. Moreover, we
found a positive correlation between IL-1 and IL-8. These
data suggest that, in lung tumors, IL-1 may influence the production of IL-8.
We observed that IL-1 mRNA was undetectable both in
the cell lines (33) and in tumors, suggesting that the neoplastic
cells are not the cellular source of IL-1. This is supported by
the observation that in tumor specimens IL-1 immunoreactivity was detected only in mononuclear cells. Because it has
been observed that IL-8 induces the production of IL-1 in
mononuclear cells in vitro and in vivo (34, 35), it cannot be excluded that IL-8 may in turn upregulate the production of IL-1 in nontumor cells. Thus, the positive correlation between
IL-1 and IL-8 could be explained hypothesizing a reciprocal
paracrine interaction between mononuclear and neoplastic
cells. A fuller understanding of the autocrine and paracrine
growth pathways influencing tumor progression could lead to
a more effective approach to tumor therapy.
| |
Footnotes |
|---|
Correspondence and requests for reprints should be addressed to Antonella Colasante, Consorzio Mario Negri Sud, Via Nazionale 66030-Santa Maria Imbaro, Chieti, Italy.
(Received in original form January 31, 1997 and in revised form April 30, 1997).
Acknowledgments: The writers thank Mr. T. D'Antuono for excellent technical assistance, Dr. A. Mantovani for the anti-IL8 and -IL-1 antibodies, Drs. A. Stoppacciaro and M. Piantelli for helpful suggestions, and Dr. F. O. Ranelletti for reviewing the manuscript.
Supported in part by grants from Ministero della Università e della Ricerca Scientifica e Tecnologica, Istituto Superiore di Sanità (Seventh Research Project on AIDS) and Associazione Italiana per la Ricerca sul Cancro.
| |
References |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1. Carney, D. N.. 1992. The biology of lung cancer. Curr. Opin. Oncol. 4: 292-298 [Medline].
2.
Bunn, B. A..
1994.
Future direction in clinical research for lung cancer.
Chest
106(Suppl.):
329-407
3. Strieter, R. M., P. J. Polverini, D. A. Arenberg, A. Walz, G. Opdenakker, J. Van Damme, and S. L. Kunkel. 1995. Role of C-X-C chemochines as regulators of angiogenesis in lung cancer. J. Leukoc. Biol. 57: 752-762 [Abstract].
4.
Massagué, J..
1990.
The transforming growth factor family.
Annu. Rev.
Cell. Biol.
6:
597-641
.
5.
Huang, F.,
E. Newman,
D. Theodorescu,
R. S. Kerbel, and
E. Friedman.
1995.
Transforming growth factor 1 (TGF1) is an autocrine positive
regulator of colon carcinoma U9 cells in vivo as shown by transfection of
a TGF1 antisense expession plasmid.
Cell. Growth Differ.
6:
1635-1642
[Abstract].
6.
Roberts, A. B.,
M. B. Sporn,
R. K. Assoian,
J. M. Smith,
N. S. Roche,
L. A. Wakefield,
U. I. Heine,
L. A. Liotta,
V. Falanga,
J. H. Kehrl, and
A. S. Fauci.
1986.
Transforming growth factor : rapid induction
of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.
Proc. Natl. Acad. Sci. U.S.A.
83:
4167-4171
7.
Yang, E. Y., and
H. L. Moses.
1990.
Transforming growth factor 1 induces changes on cell migration, proliferation and angiogenesis in the
chicken chorioallantoic membrane.
J. Cell Biol.
111:
731-741
8.
Welch, D. R.,
A. Fabra, and
M. Nakajima.
1990.
Transforming growth
factor stimulate mammary adenocarcinoma cell invasion and metastatic potential.
Proc. Natl. Acad. Sci. USA
87:
7678-7682
9.
Samuel, S. K.,
R. A. R. Hurta,
P. Kondaiah,
N. Khalil,
E. A. Turley,
J. A. Wright, and
A. H. Greenberg.
1992.
Autocrine induction of tumor
protease production and invasion by metallothionein-regulated TGF-1 (Ser223, 225).
EMBO J.
11:
1599-1605
[Medline].
10.
Steiner, M. S., and
E. R. Barrack.
1992.
Transforming growth factor 1
overproduction in prostate cancer: effects on growth in vivo and in
vitro.
Mol. Endocrinol.
6:
15-25
11.
Espevik, T.,
I. S. Figari,
M. R. Shalaby,
G. A. Lackides,
G. D. Lewis,
H. M. Shepard, and
M. A. Palladino Jr..
1987.
Inhibition of cytokine
production by cyclosporin A and transforming growth factor .
J.
Exp. Med.
166:
571-576
12. McCartney-Francis, N. L., and S. M. Wahl. 1994. Transforming growth factor beta: a matter of life and death. J. Leukoc. Biol. 55: 401-409 [Abstract].
13.
Jettern, A. M.,
J. E. Shirley, and
G. Stoner.
1986.
Regulation of proliferation and differentiation of respiratory tract epithelial cells by TGF.
Exp. Cell Res.
167:
539-549
[Medline].
14. Soderdahl, G., C. Betsholtz, A. Johansson, K. Nilsson, and J. Nergh. 1988. Differential expression of platelet-derived growth factor and transforming growth factor genes in small- and non-small-cell human lung carcinoma lines. Int. J. Cancer 41: 636-641 [Medline].
15.
Jakowlew, S. B.,
A. Mathias,
P. Chung, and
T. W. Moody.
1995.
Expression of Transforming growth factor ligand and receptor messenger
RNAs in lung cancer cell lines.
Cell Growth Differ.
6:
465-476
[Abstract].
16.
Takanami, I.,
T. Imamura,
T. Hashizume,
K. Kikuchi,
Y. Yamamoto, and
S. Kodaira.
1994.
Transforming growth factor 1 as a prognostic
factor in pulmonary adenocarcinoma.
J. Clin. Pathol.
47:
1098-1100
17. Standiford, T. J., S. L. Kunkel, M. A. Basha, S. W. Chensue, J. P. Lynch, G. B. Toews, and R. M. Strieter. 1990. Interleukin-8 gene expression by a pulmonary epithelial cell line: a model for cytokine networks in the lung. J. Clin. Invest. 86: 1945-1953 .
18. Mizuno, K., S. Sone, E. Orino, N. Mukaida, K. Matsushima, and T. Ogura. 1994. Spontaneous production of Interleukin-8 by human lung cancer cells and its augmentation by tumor necrosis factor alpha and interleukin-1 at protein and mRNA levels. Oncology 51: 467-471 [Medline].
19.
Smith, D. R.,
P. J. Polverini,
S. L. Kunkel,
M. B. Orringer,
R. I. Whyte,
M. D. Burdick,
C. A. Wilke, and
R. M. Strieter.
1994.
Inhibition of interleukin 8 attenuates angiogenesis in bronchogenic carcinoma.
J.
Exp. Med.
179:
1409-1415
20. Arenberg, D. A., S. L. Kunkel, P. J. Polverini, M. Glass, M. D. Burdick, and R. M. Strieter. 1996. Inhibition of interleukin-8 reduces tumorigenesis of human non-small cell lung cancer in SCID mice. J. Clin. Invest. 97: 2792-2802 [Medline].
21.
Dinarello, C. A..
1996.
Biologic basis for interleukin-1 in disease.
Blood
87:
2095-2147
22.
Phan, S. H.,
M. Gharraee-kermani,
B. McGarry,
S. L. Kunkel, and
F. W. Wolber.
1992.
Regulation of rat pulmonary artery endothelial cell
transforming growth factor production by IL-1 and tumor necrosis
factor-.
J. Immunol.
149:
103-106
[Abstract].
23.
Yue, T. L.,
X. K. Wang,
B. Olson, and
G. Feuerstein.
1994.
Interleukin-1 (IL-1) induces transforming growth factor 1 (TGF1) production by rat aortic smooth muscle cells.
Biochem. Biophys. Res. Commun.
204:
1186-1192
[Medline].
24. Oppenheim, J. J., C. O. C. Zachariae, N. Mukaida, and K. Matsushima. 1991. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu. Rev. Immunol. 9: 617-648 [Medline].
25.
Nakamura, H.,
K. Yoshimura,
H. A. Jaffe, and
R. C. Crystal.
1991.
Inteleukin 8 gene expression in human bronchial epithelial cells.
J. Biol.
Chem.
266:
19611-19617
26. Kwon, O. J., B. T. Au, P. D. Collins, J. N. Baraniuk, M. Adcock, K. F. Chung, and P. J. Barnes. 1994. Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells. Immunology 81: 389-394 [Medline].
27.
Matsushima, K.,
K. Morishita,
T. Yoshimura,
S. Tavu,
Y. Kobayashi,
W. Lew,
E. Appella,
H. E. Kung,
E. Leonard, and
J. J. Oppenheim.
1988.
Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNFC mRNA by interleukin-1 and tumor necrosis factor.
J. Exp. Med.
167:
1883-1893
28. Ausbel, F. M., R. Brent, R. E. Kingston, D. D. Moore, J. G. Seidman, J. A. Smith, and K. Struhl. 1990. Current Protocols in Molecular Biology. Greene Publishing Associates and Wiley Interscience, New York. 4.9.12-4.9.14.
29.
Miyazono, K.,
A. Olofsson,
P. Colosetti, and
C. H. Heldin.
1991.
A role
of the latent TGF-1-binding protein in the assembly and secretion of
TGF-1.
EMBO J.
10:
1091-1101
[Medline].
30.
Romeo, D. S.,
K. Park,
A. B. Roberts,
M. B. Sporn, and
S. J. Kim.
1993.
An element of the transforming growth factor- 1 5'-untranslated region represses translation and specificaly binds a cytosolic factor.
Mol. Endocrinol.
7:
759-766
31.
Grosch, S. M.,
V. A. Memoli,
T. A. Stukel,
L. I. Gold, and
B. A. Arrick.
1992.
Immunohistochemical staining for transforming growth factor
beta 1 associates with disease progression in human breast cancer.
Cancer Res.
52:
6949-6952
32.
Friess, H.,
Y. Yamanaka,
M. Buchler,
M. Ebert,
H. G. Beger,
L. Gold, and
M. Korc.
1993.
Enhanced expression of transforming growth factor isoforms in pancreatic cancer correlates with decreased survival.
Gastroenterology
105:
1846-1856
[Medline].
33. Colasante, A., G. Castrilli, F. B. Aiello, M. Brunetti, and P. Musiani. 1995. Role of cytokines in distribution and differentiation of dendritic cell/Langerhans' cell lineage in human primary carcinomas of the lung. Hum. Pathol. 26: 866-872 [Medline].
34.
Yu, C. L.,
K. U. Sun,
S. C. Shei,
C. Y. Tsai,
S. T. Tsai,
J. C. Wang,
T. S. Liao,
W. M. Lin,
H. L. Chen,
H. S. Yu, and
S. H. Han.
1994.
Interleukin-8 modulates interleukin-1, interleukin-6 and tumor necrosis factor- release from normal human mononuclear cells.
Immunopharmacology
27:
207-24
[Medline].
35. Matsukawa, A., T. Yoshimura, T. Maeda, S. Ohkawara, K. Takagi, and M. Yoshinaga. 1995. Neutrophil accumulation and activation by homologous IL-8 in rabbits. IL-8 induces destruction of cartilage and production of IL-1 and IL-1 receptor antagonist in vivo. J. Immunol. 154: 5418-5425 [Abstract].
This article has been cited by other articles:
 |
|
 |
|
  M. Pold, L. X. Zhu, S. Sharma, M. D. Burdick, Y. Lin, P. P. N. Lee, A. Pold, J. Luo, K. Krysan, M. Dohadwala, et al. Cyclooxygenase-2-Dependent Expression of Angiogenic CXC Chemokines ENA-78/CXC Ligand (CXCL) 5 and Interleukin-8/CXCL8 in Human Non-Small Cell Lung Cancer Cancer Res., March 1, 2004; 64(5): 1853 - 1860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Haqqani, J. K. Sandhu, and H.C. Birnboim Constitutive expression of interleukin-8 by Mutatect cells markedly affects their tumor biology Carcinogenesis, February 1, 2001; 22(2): 243 - 250. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Proc. Am. Thorac. Soc. | Am. J. Respir. Cell Mol. Biol. |