Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4
Open accessAbstract
Interleukin 4 (also known as "B cell stimulatory factor-1"), a cytokine product of T lymphocytes and mast cells, stimulates synthesis of the extracellular matrix proteins, types I and III collagen and fibronectin, by human dermal fibroblasts in vitro. Stimulation of collagen by human recombinant (hr)IL-4 was also demonstrated in several fibroblastic synovial cell lines obtained from patients with rheumatoid arthritis and osteoarthritis. The stimulatory effect of hrIL-4 on fibroblast collagen synthesis was specifically neutralized by rabbit anti-hrIL-4 Ig. IL-4 specifically increased the steady-state levels of types I and III procollagen and fibronectin mRNAs, with no effect on cytoplasmic beta-actin mRNA. Quantitative analysis of the levels of Pro alpha 1(I) collagen transcripts in IL-4-treated fibroblast cultures was also corroborated by antisense RNA-mRNA hybridization and RNAse resistant hybrids which showed that IL-4-treated fibroblasts expressed higher levels of Pro alpha 1(I) collagen transcripts. Nuclear run-off transcription experiments indicated that IL-4 stimulated the rates of mRNA biogenesis. Based on these observations we conclude that IL-4 exerts its effect on collagen and fibronectin synthesis at the pretranslational level, resulting in synthesis of these extracellular matrix proteins. These and other data suggest that IL-4 may be a "fibrogenic cytokine" that could be important in promoting biogenesis of extracellular matrix proteins in normal wound healing and in pathological fibrosis in which mast cells and T lymphocytes play a central role.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Detection of Th2 cells and their secretory mediators is enhanced in the lungs and blood of patients with IPF.
“detection of Th2 cells and their secretory mediators appears to be enhanced in the lungs and blood of patients with IPF (137–140).”
From The Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis (2018) · cites this paper as [138]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Melton, D. A., Krieg, P. A., Rebagliati, M. R., Maniatis, T., Zinn, K., & Green, M. R. (1984) · Nucleic Acids Research · doi:10.1093/nar/12.18.7035 · Cited by 6,324 · see citing works
[18] Hybridization of denatured RNA transferred or dotted to nitrocellulose paper
Thomas, P. S. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)00060-9 · Cited by 1,102 · see citing works
Identification of a T cell-derived b cell growth factor distinct from interleukin 2.
Howard, M., Farrar, J., Hilfiker, M. L., Johnson, B., Takatsu, K., Hamaoka, T., & Paul, W. E. (1982) · The Journal of Experimental Medicine · doi:10.1084/jem.155.3.914 · Cited by 1,099 · see citing works
B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells.
Coffman, R. L., Ohara, J., Bond, M. W., Carty, J., Zlotnik, A., & Paul, W. E. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.12.4538 · Cited by 796 · see citing works
Lee, F. H. H., Yokota, T., Otsuka, T., Meyerson, P., Villaret, D. B., Coffman, R. L., Mosmann, T. R., Rennick, D. M., Roehm, N. W., & Smith, C. A. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.7.2061 · Cited by 524 · see citing works
Yokota, T., Otsuka, T., Mosmann, T. R., Banchereau, J., Defrance, T., Blanchard, D., de Vries, J. E., Lee, F., & Arai, K. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.16.5894 · Cited by 501 · see citing works
Chu, M., Myers, J. C., Bernard, M. P., Ding, J.-F., & Ramirez, F. (1982) · Nucleic Acids Research · doi:10.1093/nar/10.19.5925 · Cited by 492 · see citing works
Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter
Noma, Y., Sideras, P., Naito, T., Bergstedt‐Lindqvist, S., Azuma, C., Gronowicz, E. S., Tanabe, T., Kinashi, T., Matsuda, F., Yaoita, Y., et al. (1986) · Nature · doi:10.1038/319640a0 · Cited by 479 · see citing works
Increased expression of Ia antigens on resting B cells: an additional role for B-cell growth factor.
Noelle, R. J., Krammer, P. H., Ohara, J., Uhr, J. W., & Vitetta, E. S. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.19.6149 · Cited by 437 · see citing works
Predominantly T-Cell Infiltrate in Rheumatoid Synovial Membranes
van Boxel, J. A., & Paget, S. A. (1975) · New England Journal of Medicine · doi:10.1056/nejm197509112931101 · Cited by 387 · see citing works
Lymphocytes in the skin of patients with progressive systemic sclerosis
Roumm, A. D., Whiteside, T. L., Medsger, T. A., & Rodnan, G. P. (1984) · Arthritis & Rheumatism · doi:10.1002/art.1780270607 · Cited by 378 · see citing works
Needleman, B. W., Wigley, F. M., & Stair, R. W. (1992) · Arthritis & Rheumatism · doi:10.1002/art.1780350111 · Cited by 304 · see citing works
Interleukin-induced increase in Ia expression by normal mouse B cells.
Roehm, N. W., Leibson, H. J., Zlotnik, A., Kappler, J. W., Marrack, P., & Cambier, J. C. (1984) · The Journal of Experimental Medicine · doi:10.1084/jem.160.3.679 · Cited by 292 · see citing works
Receptors for B-cell stimulatory factor-1 expressed on cells of haematopoietic lineage
Ohara, J., & Paul, W. E. (1987) · Nature · doi:10.1038/325537a0 · Cited by 281 · see citing works
Lowenthal, J. W., Castle, B. E., Christiansen, J., Schreurs, J., Rennick, D. M., Arai, N., Hoy, P., Takebe, Y., & Howard, M. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.140.2.456 · Cited by 242 · see citing works
Chronic graft versus host disease: A syndrome of disordered immunity
Graze, P. R., & Gale, R. P. (1979) · The American Journal of Medicine · doi:10.1016/0002-9343(79)91171-9 · Cited by 241 · see citing works
Characterization of the human B cell stimulatory factor 1 receptor.
Park, L. S., Friend, D. J., Sassenfeld, H. M., & Urdal, D. L. (1987) · The Journal of Experimental Medicine · doi:10.1084/jem.166.2.476 · Cited by 224 · see citing works
Grabstein, K. H., Eisenman, J. R., Mochizuki, D. Y., Shanebeck, K. D., Conlon, P. J., Hopp, T. P., March, C. J., & Gillis, S. A. (1986) · The Journal of Experimental Medicine · doi:10.1084/jem.163.6.1405 · Cited by 182 · see citing works
Postlethwaite, A. E., & Seyer, J. M. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115247 · Cited by 139 · see citing works
Self-citationPostlethwaite, A. E., Smith, G. N., Mainardi, C. L., Seyer, J. M., & Kang, A. H. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.132.5.2470 · Cited by 137 · see citing works
Self-citationRaghow, R., Gossage, D. L., & Kang, A. H. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)38555-1 · Cited by 113 · see citing works
Self-citationWood, D. D., Bayne, E. K., Goldring, M. B., et al. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.134.2.895 · Cited by 112 · see citing works
T Cell‐Derived Lymphokines That Induce IgM and IgG Secretion in Activated Murine B Cells
Vitetta, E. S., Brooks, K. H., Chen, Y. W., Isakson, P. C., Jones, S., Layton, J. E., Mishra, G. C., Puré, E., Weiss, E. A., Word, C. J., et al. (1984) · Immunological Reviews · doi:10.1111/j.1600-065x.1984.tb00480.x · Cited by 106 · see citing works
Lymphokine regulation of inflammatory processes: Interleukin-4 stimulates fibroblast proliferation
Monroe, J. G., Haldar, S., Prystowsky, M. B., et al. (1988) · Clinical Immunology and Immunopathology · doi:10.1016/0090-1229(88)90119-5 · Cited by 103 · see citing works
Aycock, R. S., Raghow, R., Stricklin, G. P., et al. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67026-7 · Cited by 82 · see citing works
Self-citationPartial biochemical characterization of IgG1‐inducing factor
Sideras, P., Bergstedt‐Lindqvist, S., & Severinson, E. (1985) · European Journal of Immunology · doi:10.1002/eji.1830150612 · Cited by 70 · see citing works
Raghow, R., Gossage, D. L., Seyer, J. M., et al. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)90805-7 · Cited by 59 · see citing works
Self-citationMast cells and fibrosis. The relevance to scleroderma.
Claman, H. N. (1990) · PubMed · Cited by 47 · see citing works
The Lymphocytic Infiltrative Lung Diseases
Vath, R. R., Alexander, C. B., & Fulmer, J. D. (1982) · Clinics in Chest Medicine · doi:10.1016/s0272-5231(21)00171-4 · Cited by 36 · see citing works
Antiimmunoglobulin-treated B cells respond to a B cell differentiation factor for IgG1.
Isakson, P. C. (1986) · The Journal of Experimental Medicine · doi:10.1084/jem.164.1.303 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Inflammatory Cytokines in the BAL of Patients With ARDS
Meduri, G. U., Kohler, G., Headley, S., Tolley, E., Stentz, F., & Postlethwaite, A. (1995) · Chest · doi:10.1378/chest.108.5.1303 · Cited by 695 · see citing works
Self-citationThe Role of Immune and Inflammatory Cells in Idiopathic Pulmonary Fibrosis
Desai, O., Winkler, J., Minasyan, M., & Herzog, E. L. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00043 · Cited by 314 · see citing works
Gratchev, A., Guillot, P., Hakiy, N., Politz, O., Orfanos, C. E., Schledzewski, K., & Goerdt, S. (2001) · Scandinavian Journal of Immunology · doi:10.1046/j.1365-3083.2001.00885.x · Cited by 300 · see citing works
McNally, A. K., & Anderson, J. M. (2002) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64882-1 · Cited by 225 · see citing works
T cells in systemic sclerosis: a reappraisal
O'Reilly, S., Hugle, T., & van Laar, J. M. (2012) · Rheumatology · doi:10.1093/rheumatology/kes090 · Cited by 218 · see citing works
Hashimoto, S., Gon, Y., Takeshita, I., Maruoka, S., & Horie, T. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.114702 · Cited by 151 · see citing works
Vascular involvement in systemic sclerosis (scleroderma)
Postlethwaite, Pattanaik, D., & Brown, M. (2011) · Journal of Inflammation Research · doi:10.2147/jir.s18145 · Cited by 119 · see citing works
Antagonistic Effects of Interferon-γ and Interleukin-4 on Fibroblast Cultures.
Serpier, H., Gillery, P., Salmon-Ehr, V., Garnotel, R., Georges, N., Kalis, B., & Maquart, F.-X. (1997) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12319207 · Cited by 88 · see citing works
Th2 cytokine regulation of type I collagen gel contraction mediated by human lung mesenchymal cells
Liu, X., Kohyama, T., Wang, H., Zhu, Y. K., Wen, F.-Q., Kim, H. J., Romberger, D. J., & Rennard, S. I. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00321.2001 · Cited by 77 · see citing works
Overexpression of the transcription factor GATA-3 enhances the development of pulmonary fibrosis
Kimura, T., Ishii, Y., Yoh, K., Morishima, Y., Iizuka, T., Kiwamoto, T., Matsuno, Y., Homma, S., Nomura, A., Sakamoto, T., et al. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.051160 · Cited by 55 · see citing works
- Authors
- Postlethwaite, A. E., Holness, M. A., Katai, H., & Raghow, R.
- Affiliations
- University of Tennessee Health Science Center (US)
- Veterans Health Administration (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1992-10-01
- Volume
- 90
- Issue
- 4
- Pages
- 1479-1485
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC443194
- OpenAlex
- W2049706385
- Cited by
- 504
- References
- 30
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 8 · 2023: 12 · 2022: 9 · 2021: 13 · 2020: 8 · 2019: 10 · 2018: 8 · 2017: 14 · 2016: 13 · 2015: 15 · 2014: 9 · 2013: 12 · 2012: 11
- FWCI
- 20.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health (5r01ar026034-13)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50AR039166, AR39166, AR 26034)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- IL-4, dermal fibroblasts, extracellular matrix proteins, collagen synthesis, type I collagen, type III collagen, fibronectin, procollagen mRNA, rheumatoid arthritis, osteoarthritis, synovial fibroblasts, fibrosis, wound healing, mast cells, T cells
- MeSH terms
- Cells, Cultured, Collagen, Fibroblasts, Fibronectins, Humans, Procollagen, Recombinant Proteins, RNA, Messenger, Interleukin-4
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review