| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Mediates TNF-
Inhibitory Effect on 2(I) Collagen (COL1A2) Gene Transcription in Human Dermal Fibroblasts1
,
,
Departments of
*
Dermatology and Cutaneous Biology and
Biochemistry and Molecular Pharmacology, Jefferson Medical College, and
Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, PA 19107; and
§
Department of Dermatology, Yonsei University College of Medicine, Seoul, Korea
Among its plethora of activities as an inflammatory mediator,
TNF-
has potent regulatory control on extracellular matrix
production and degradation. Earlier studies have documented that
TNF- inhibits type I collagen gene (COL1A2) expression at the
transcriptional level, but the characterization of the transcription
factors involved has been elusive. In the present study, using
transient cell transfection of human dermal fibroblasts with a battery
of 5' end deletion/chloramphenicol acetyltransferase (CAT) reporter
gene constructs, we have characterized the TNF- response element of
the COL1A2 promoter. The TNF- response element was attributed to a
specific region that comprises noncanonical activator protein-1 (AP-1)
(CGAGTCA) and NF-
B (AGAGTTTCCC) binding sites. TNF- effect was
eliminated by a 2-bp substitution mutation in the NF-B1 binding half
site of the NF-B cis element. Electrophoretic
mobility shift assays (EMSA) showed that recombinant human NF-B
heterodimers as well as NF-B1 and RelA homodimers, but not AP-1,
were capable of binding this element. Further, EMSA with human
fibroblast nuclear extracts demonstrated enhanced binding of a single,
specific complex within 5 min of TNF- stimulation, which reached a
plateau by 1 h and was not affected by preincubation of cells with
cycloheximide. Gel supershift assays identified the complex as the
NF-B (p50/p65) heterodimer, whereas Abs to nuclear factor of
activated T cells (NF-AT) and Jun family members failed to recognize
the complex. These data suggest that in fibroblasts TNF- activates
and initiates the nuclear translocation of NF-B that binds a
divergent NF-B element and plays a critical role in the observed
inhibition of 2(I) collagen gene
transcription.
This article has been cited by other articles:
|
|
 |
|
  T. Miyake, M. Aoki, H. Masaki, T. Kawasaki, M. Oishi, K. Kataoka, T. Ogihara, Y. Kaneda, and R. Morishita Regression of Abdominal Aortic Aneurysms by Simultaneous Inhibition of Nuclear Factor {kappa}B and Ets in a Rabbit Model Circ. Res., November 26, 2007; 101(11): 1175 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Miltyk, E. Karna, and J. A. Palka Prolidase-Independent Mechanism of Camptothecin-Induced Inhibition of Collagen Biosynthesis in Cultured Human Skin Fibroblasts J. Biochem., February 1, 2007; 141(2): 287 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Durand, V. Flacher, A. Romeas, F. Carrouel, E. Colomb, C. Vincent, H. Magloire, M.-L. Couble, F. Bleicher, M.-J. Staquet, et al. Lipoteichoic Acid Increases TLR and Functional Chemokine Expression while Reducing Dentin Formation in In Vitro Differentiated Human Odontoblasts. J. Immunol., March 1, 2006; 176(5): 2880 - 2887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Sohn, C. B. Deming, D. C. Johns, H. C. Champion, C. Bian, K. Gardner, and J. J. Rade Regulation of endothelial thrombomodulin expression by inflammatory cytokines is mediated by activation of nuclear factor-kappa B Blood, May 15, 2005; 105(10): 3910 - 3917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tanaka, T. T. Antoniv, K. Liu, L. Wang, D. J. Wells, F. Ramirez, and G. Bou-Gharios Cooperativity between Far Upstream Enhancer and Proximal Promoter Elements of the Human {alpha}2(I) Collagen (COL1A2) Gene Instructs Tissue Specificity in Transgenic Mice J. Biol. Chem., December 31, 2004; 279(53): 56024 - 56031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Novitskiy, J. J. Potter, L. Rennie-Tankersley, and E. Mezey Identification of a Novel NF-{kappa}B-binding Site with Regulation of the Murine {alpha}2(I) Collagen Promoter J. Biol. Chem., April 9, 2004; 279(15): 15639 - 15644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kubo, J. Czuwara-Ladykowska, O. Moussa, M. Markiewicz, E. Smith, R. M. Silver, S. Jablonska, M. Blaszczyk, D. K. Watson, and M. Trojanowska Persistent Down-Regulation of Fli1, a Suppressor of Collagen Transcription, in Fibrotic Scleroderma Skin Am. J. Pathol., August 1, 2003; 163(2): 571 - 581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Higashi, Y. Inagaki, N. Suzuki, S. Mitsui, A. Mauviel, H. Kaneko, and I. Nakatsuka Y-box-binding Protein YB-1 Mediates Transcriptional Repression of Human alpha 2(I) Collagen Gene Expression by Interferon-gamma J. Biol. Chem., February 7, 2003; 278(7): 5156 - 5162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Luchetti, P. Paroncini, P. Majlingova, J. Frampton, M. Mucenski, S. S. Baroni, P. Sambo, J. Golay, M. Introna, and A. Gabrielli Characterization of the c-Myb-responsive Region and Regulation of the Human Type I Collagen alpha 2 Chain Gene by c-Myb J. Biol. Chem., January 10, 2003; 278(3): 1533 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. K. Sengupta, J. Fargo, and B. D. Smith The RFX Family Interacts at the Collagen (COL1A2) Start Site and Represses Transcription J. Biol. Chem., July 5, 2002; 277(28): 24926 - 24937. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Ghosh Factors Involved in the Regulation of Type I Collagen Gene Expression: Implication in Fibrosis Experimental Biology and Medicine, May 1, 2002; 227(5): 301 - 314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Vermes, R. Chandrasekaran, J. J. Jacobs, J. O. Galante, K. A. Roebuck, and T. T. Glant The Effects of Particulate Wear Debris, Cytokines, and Growth Factors on the Functions of MG-63 Osteoblasts J. Bone Joint Surg. Am., February 1, 2001; 83(2): 201 - 201. [Abstract] [Full Text]
|
|
|
|
|
|
F. Verrecchia, M. Pessah, A. Atfi, and A. Mauviel Tumor Necrosis Factor-alpha Inhibits Transforming Growth Factor-beta /Smad Signaling in Human Dermal Fibroblasts via AP-1 Activation J. Biol. Chem., September 22, 2000; 275(39): 30226 - 30231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Czuwara-Ladykowska, F. Shirasaki, P. Jackers, D. K. Watson, and M. Trojanowska Fli-1 Inhibits Collagen Type I Production in Dermal Fibroblasts via an Sp1-dependent Pathway J. Biol. Chem., June 8, 2001; 276(24): 20839 - 20848. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
