The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Interferon beta‐1b inhibits gelatinase secretion and in vitro migration of human T cells: A possible mechanism for treatment efficacy in multiple sclerosis
Abstract
Treatment with interferon beta‐1b has substantial clinical benefit in the demyelinating disease multiple sclerosis, yet the mechanism of action in the disease remains largely unknown. Gelatinase A (matrix metalloproteinase‐2, 72‐kd gelatinase) and B (matrix metalloproteinase‐9, 92‐kd gelatinase) are matrix metalloproteinases capable of enzymatic digestion of subendothelial basement membrane constituents. In human T cells, interleukin‐2 induces gelatinase secretion and enhances gelatinase‐dependent migration across an artificial basement membrane‐like layer in vitro. Pretreatment of T cells with interferon beta‐lb for 48 hours decreased interleukin‐2‐induced gelatinase production and secretion as determined by zymography. In parallel to the downregulation of gelatinase secretion, pretreatment with interferon beta‐lb inhibited T‐cell migration across the basement membrane in vitro by up to 90%, but had only a minor impact on cell locomotion per se. For both gelatinase secretion and T‐cell migration, the inhibitory effect mediated by exposure to interferon beta‐1b was dose dependent. Fluorescence‐activated cell sorter analysis also showed that interferon beta‐1b downregulates the interleukin‐2 receptor α‐chain and lowered the affinity of interleukin‐2 to the cell surface by 30%, which may represent an additional mechanism for the observed effects of interferon beta‐1b. The dramatic effects of interferon beta‐1b on gelatinase expression and migration raise the possibility that its beneficial effects in multiple sclerosis may result from interference with the capacity of activated T cells to traverse the basement membrane and migrate to the central nervous system.
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Cites
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Cited by
Interferons, interferon‐like cytokines, and their receptors
Pestka, S., Krause, C. D., & Walter, M. R. (2004) · Immunological Reviews · doi:10.1111/j.0105-2896.2004.00204.x · Cited by 1,766
Interferons at age 50: past, current and future impact on biomedicine
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Matrix metalloproteinases and diseases of the CNS
Wee Yong, V., Forsyth, P. A., Bell, R., Krekoski, C. A., & Edwards, D. R. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01169-7 · Cited by 639
Metalloproteinases: Mediators of Pathology and Regeneration in the CNS
Yong, V. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1807 · Cited by 582
Targeting leukocyte MMPs and transmigration
Brundula, V., Rewcastle, N. B., Metz, L. M., Bernard, C. C., & Yong, V. W. (2002) · Brain · doi:10.1093/brain/awf133 · Cited by 426
Metadata
- Authors
- Leppert, D., Waubant, E., Bürk, M. R., Oksenberg, J. R., & Hauser, S. L.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1996-12
- Volume
- 40
- Issue
- 6
- Pages
- 846-852
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W1968168664
- Cited by
- 291
- References
- 25
- FWCI
- 16.02
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Interferon beta‐1b inhibits gelatinase secretion and in vitro migration of human T cells: A possible mechanism for treatment efficacy in multiple sclerosis. https://app.cochat.ai/papers/10.1002/ana.410400606
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- Leppert, D., Waubant, E., Bürk, M. R., Oksenberg, J. R., & Hauser, S. L. (1996). Interferon beta‐1b inhibits gelatinase secretion and in vitro migration of human T cells: A possible mechanism for treatment efficacy in multiple sclerosis. Annals of Neurology. https://doi.org/10.1002/ana.410400606
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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